Favilla, Christopher G.; Parthasarathy, Ashwin B.; Detre, John A.; Yodh, Arjun G.; Mullen, Michael T.; Kasner, Scott E.; Gannon, Kimberly; Messé, Steven R.
Optimization of cerebral blood flow (CBF) is the cornerstone of clinical management in a number of neurologic diseases, most notably ischemic stroke. Intrathoracic pressure influences cardiac output and has the potential to impact CBF. Here, we aim to quantify cerebral hemodynamic changes in response to increased respiratory impedance (RI) using a non-invasive respiratory device. We measured cerebral perfusion under varying levels of RI (6 cm H2O, 9 cm H2O, and 12 cm H2O) in 20 healthy volunteers. Simultaneous measurements of microvascular CBF and middle cerebral artery mean flow velocity (MFV), respectively, were performed with optical diffuse correlation spectroscopy and transcranial Doppler ultrasound. At a high level of RI, MFV increased by 6.4% compared to baseline (p = 0.004), but changes in cortical CBF were non-significant. In a multivariable linear regression model accounting for end-tidal CO2, RI was associated with increases in both MFV (coefficient: 0.49, p < 0.001) and cortical CBF (coefficient: 0.13, p < 0.001), although the magnitude of the effect was small. Manipulating intrathoracic pressure via non-invasive RI was well tolerated and produced a small but measurable increase in cerebral perfusion in healthy individuals. Future studies in acute ischemic stroke patients with impaired cerebral autoregulation are warranted in order to assess whether RI is feasible as a novel non-invasive therapy for stroke. PMID:28261153
INVASIVE BLOOD FLOW MONITORING ON THE WRIST M. Maier, L-G. Lindberg Department of Biomedical Engineering , University of Linköping, Sweden The Swedish...Department of Biomedical Engineering . This study was supported by The Swedish Competence Center of Non-invasive Medical Measurements NIMED...Element Number Author(s) Project Number Task Number Work Unit Number Performing Organization Name(s) and Address(es) Department of Biomedical
Kalchenko, Vyacheslav; Brill, Alexander; Fine, Ilya; Harmelin, Alon
Physiological blood coagulation is an essential biological process. Current tests for plasma coagulation (clotting) need to be performed ex vivo and require fresh blood sampling for every test. A recently published work describes a new, noninvasive, in vivo approach to assess blood coagulation status during mechanical occlusion1. For this purpose, we have tested this approach and applied a controlled laser beam to blood micro-vessels of the mouse ear during mechanical occlusion. Standard setup for intravital transillumination videomicroscopy and laser based imaging techniques were used for monitoring the blood clotting process. Temporal mechanical occlusion of blood vessels in the observed area was applied to ensure blood flow cessation. Subsequently, laser irradiation was used to induce vascular micro-injury. Changes in the vessel wall, as well as in the pattern of blood flow, predispose the area to vascular thrombosis, according to the paradigm of Virchow's triad. In our experiments, two elements of Virchow's triad were used to induce the process of clotting in vivo, and to assess it optically. We identified several parameters that can serve as markers of the blood clotting process in vivo. These include changes in light absorption in the area of illumination, as well as changes in the pattern of the red blood cells' micro-movement in the vessels where blood flow is completely arrested. Thus, our results indicate that blood coagulation status can be characterized by non-invasive, in vivo methodologies.
Wang, Xi; Pestov, Dmitry; Zhang, Aihua; Murawski, Robert; Sokolov, Alexei; Welch, George; Laane, Jaan; Scully, Marlan
We develop a spectroscopy technique that combines the advantages of both the frequency-resolved coherent anti-Stokes Raman scattering (CARS) and the time-resolved CARS. We use broadband preparation pulses to get an instantaneous coherent excitation of multiplex molecular vibration levels and subsequent optically shaped time-delayed narrowband probing pulse to detect these vibrations. This technique can suppress the nonresonant background and retrieve the molecular fingerprint signal efficiently and rapidly. We employ this technique to glucose detection, the final goal of which is accurate, non-invasive (i.e. painless) and continuous monitoring of blood glucose concentration in the Diabetes diagnosis to replace the current glucose measurement process, which requires painful fingerpricks and therefore cannot be performed more than a few times a day. We have gotten the CARS spectra of glucose aqueous solution down to 2 mM.
Woo, Sung Hun; Choi, Yun Young; Kim, Dae Jung; Bien, Franklin; Kim, Jae Joon
Accurate continuous direct measurement of the blood pressure is currently available thru direct invasive methods via intravascular needles, and is mostly limited to use during surgical procedures or in the intensive care unit (ICU). Non-invasive methods that are mostly based on auscultation or cuff oscillometric principles do provide relatively accurate measurement of blood pressure. However, they mostly involve physical inconveniences such as pressure or stress on the human body. Here, we introduce a new non-invasive mechanism of tissue-informative measurement, where an experimental phenomenon called subcutaneous tissue pressure equilibrium is revealed and related for application in detection of absolute blood pressure. A prototype was experimentally verified to provide an absolute blood pressure measurement by wearing a watch-type measurement module that does not cause any discomfort. This work is supposed to contribute remarkably to the advancement of continuous non-invasive mobile devices for 24-7 daily-life ambulatory blood-pressure monitoring.
Buckley, K; Atkins, C G; Chen, D; Schulze, H G; Devine, D V; Blades, M W; Turner, R F B
After being separated from (donated) whole blood, red blood cells are suspended in specially formulated additive solutions and stored (at 4 °C) in polyvinyl chloride (PVC) blood-bags until they are needed for transfusion. With time, the prepared red cell concentrate (RCC) is known to undergo biochemical changes that lower effectiveness of the transfusion, and thus regulations are in place that limit the storage period to 42 days. At present, RCC is not subjected to analytical testing prior to transfusion. In this study, we use Spatially Offset Raman Spectroscopy (SORS) to probe, non-invasively, the biochemistry of RCC inside sealed blood-bags. The retrieved spectra compare well with conventional Raman spectra (of sampled aliquots) and are dominated by features associated with hemoglobin. In addition to the analytical demonstration that SORS can be used to retrieve RCC spectra from standard clinical blood-bags without breaking the sterility of the system, the data reveal interesting detail about the oxygenation-state of the stored cells themselves, namely that some blood-bags unexpectedly contain measurable amounts of deoxygenated hemoglobin after weeks of storage. The demonstration that chemical information can be obtained non-invasively using spectroscopy will enable new studies of RCC degeneration, and points the way to a Raman-based instrument for quality-control in a blood-bank or hospital setting.
Andrews, Joseph Thomas; Solanki, J.; Choudhary, Om P.; Chouksey, S.; Malvia, N.; Chaturvedi, P.; Sen, P.
Every day, about 150 Million people worldwide face the problem of diabetic metabolic control. Both the hypo- and hyper- glycaemic conditions of patients have fatal consequences and warrant blood glucose monitoring at regular interval. Existing blood glucose monitors can be widely classified into three classes viz., invasive, minimally invasive, and noninvasive. Invasive monitoring requires small volume of blood and are inappropriate for continuous monitoring of blood glucose. Minimally invasive monitors analyze tissue fluid or extract few micro litre of blood only. Also the skin injury is minimal. On the other hand, noninvasive devices are painless and void of any skin injury. We use an indigenously developed polarization sensitive Optical Coherence Tomography to measure the blood glucose levels. Current trends and recent results with the device are discussed.
Zhang, Xiqin; Ting, Choon Meng; Yeo, Joon Hock
Blood glucose level is an important parameter for doctors to diagnose and treat diabetes. The Near-Infra-Red (NIR) spectroscopy method is the most promising approach and this involves measurement on the body skin. However it is noted that the skin temperature does fluctuate with the environmental and physiological conditions and we found that temperature has important influences on the glucose measurement. In-vitro and in-vivo investigations on the temperature influence on blood glucose measurement have been carried out. The in-vitro results show that water temperature has significant influence on water absorption. Since 90% of blood components are water, skin temperature of measurement site has significant influence on blood glucose measurement. Also the skin temperature is related to the blood volume, blood volume inside capillary vessels changes with skin temperature. In this paper the relationship of skin temperature and signal from the skin and inside tissue was studied at different finger temperatures. Our OGTT (oral glucose tolerance test) trials results show the laser signals follow the skin temperature trend and the correlation of signal and skin temperature is much stronger than the correlation of signal and glucose concentration. A finger heater device is designed to heat and maintain the skin temperature of measurement site. The heater is controlled by an electronic circuit according to the skin temperature sensed by a thermocouple that is put close to the measurement site. In vivo trials were carried out and the results show that the skin temperature significantly influences the signal fluctuations caused by pulsate blood and the average signal value.
Park, Seul Gi; Lee, Oh Haeng; Park, Yong-Hee; Shin, Hwa Yong; Kang, Hyun; Baek, Chong Wha; Jung, Yong Hun
Background We hypothesized that induction of general anesthesia using sevoflurane improves the accuracy of non-invasive hemoglobin (SpHb) measurement of Masimo Radical-7® Pulse CO-Oximetry by inducing peripheral vasodilation and increasing the perfusion index (PI). The aim of this study is to investigate the change in the SpHb and the PI measured by Rad7 during induction of general anesthesia using sevoflurane. Methods The laboratory hemoglobin (Hblab) was measured before surgery by venous blood sampling. The SpHb and the PI was measured twice; before and after the induction of general anesthesia using sevoflurane. The changes of SpHb, Hbbias (Hbbias = SpHb - Hblab), and PI before and after the induction of general anesthesia were analyzed using a paired t-test. Also, a Pearson correlation coefficient analysis was used to analyze the correlation between the Hbbias and the PI. Results The SpHb and the PI were increased after the induction of general anesthesia using sevoflurane. There was a statistically significant change in the Hbbias from -2.8 to -0.7 after the induction of general anesthesia. However, the limit of agreement (2 SD) of the Hbbias did not change after the induction of general anesthesia. The Pearson correlation coefficient between the Hbbias and the PI was not statistically significant. Conclusions During induction of general anesthesia using sevoflurane, the accuracy of SpHb measurement was improved and precision was not changed. The correlation between Hbbias and PI was not significant. PMID:26257847
Lo, Y M
The non-invasive determination of fetal genetic characteristics, including blood group types, is a long-sought goal of modern genetics. Previous work on the use of fetal cells in maternal blood has been hampered by the rarity of such cells. The recent discovery of cell-tree fetal DNA in maternal blood has opened up new possibilities for non-invasive prenatal diagnosis. It is particularly useful that fetal DNA is present in relatively high concentrations in maternal plasma, making its robust detection possible using modern technology. Large-scale clinical trials and standardization of protocols still need to be carried out. However, there is optimism that the accurate and safe prenatal determination of fetal blood group types may be achieved in routine clinical practice in the near future.
arterial pressure of 40 mmHg, and then held there until experimental intervention, resuscitation, decompensation or death occurred. The experiment was...regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals...Rheoencephalography (REG) as a Non-Invasive Monitoring Alternative for the Assessment of Brain Blood Flow P3 - 12 RTO-MP-HFM-109 experiments we
Durduran, Turgut; Yodh, Arjun G.
Diffuse correlation spectroscopy (DCS) uses the temporal fluctuations of near-infrared (NIR) light to measure cerebral blood flow (CBF) non-invasively. Here, we provide a brief history of DCS applications in brain with an emphasis on the underlying physical ideas, common instrumentation and validation. Then we describe recent clinical research that employs DCS-measured CBF as a biomarker of patient well-being, and as an indicator of hemodynamic and metabolic response to functional stimuli. PMID:23770408
Ho, S S; O'Donoghue, K; Choolani, M
In Singapore, 1 in 5 pregnancies occur in mothers > 35 years old and genetic diseases, such as thalassaemia, are common. Current methods for the diagnosis of aneuploidy and monogenic disorders require invasive testing by amniocentesis, chorion villus biopsy or fetal blood sampling. These tests carry a procedure-related risk of miscarriage that is unacceptable to many couples. Development of non-invasive methods for obtaining intact fetal cells would allow accurate prenatal diagnosis for aneuploidy and single gene disorders, without the attendant risks associated with invasive testing, and would increase the uptake of prenatal diagnosis by women at risk. Isolation of fetal erythroblasts from maternal blood should allow accurate non-invasive prenatal diagnosis of both aneuploidies and monogenic disorders. Expression of gamma-globin in maternal erythroblasts and the inability to locate fetal erythroblasts reliably in all pregnancies have prevented its clinical application. In the absence of a highly specific fetal cell marker, enrichment, identification and diagnosis--the 3 components of non-invasive prenatal diagnosis--have clearly defined objectives. Since fetal cells are rare in maternal blood, the sole purpose of enrichment is yield--to recover as many fetal cells as possible--even if purity is compromised at this stage. In contrast, the primary goal of identification is specificity; absolute certainty of fetal origin is required at this stage if the ultimate objective of diagnosis, accuracy, is to be achieved. This review summarises the current state of the art of non-invasive prenatal diagnosis using fetal erythroblasts enriched from maternal blood.
Sujatha, N.; Anand, B. S. Suresh; Jayanthy, A. K.; Murthy, V. B. Narayana; Sheshadri; Poddar, Richa
Diffuse reflectance spectroscopy and laser speckle imaging have been identified as an effective tool in characterizing/assessing tissue oxygenation and blood flow in real time tissues. In this paper we are exploring the possibility of finding out blood flow/oxygenation at different areas of feet of subjects with different levels of diabetes. Tissue blood flow is determined by assessing the contrast variations in the laser speckle image of the foot and tissue oxygenation is assessed by diffuse reflectance spectroscopy. A combination of both techniques offers an effective and purely non invasive mode of examination in the staging of Diabetes.
Zhang, Yang; Zhu, Jian-Ming; Liang, Yong-Bo; Chen, Hong-Bo; Yin, Shi-Min; Chen, Zhen-Cheng
The most common method used for minimizing the occurrence of diabetes complications is frequent glucose testing to adjust the insulin dose. However, using blood glucose (BG) meters presents a risk of infection. It is of great importance to develop non-invasive BG detection techniques. To realize high-accuracy, low-cost and continuous glucose monitoring, we have developed a non-invasive BG detection system using a mixed signal processor 430 (MSP430) microcontroller. This method is based on the combination of the conservation-of-energy method with a sensor integration module, which collects physiological parameters, such as the blood oxygen saturation (SPO2), blood flow velocity and heart rate. New methods to detect the basal metabolic rate (BMR) and BV are proposed, which combine the human body heat balance and characteristic signals of photoplethysmography as well dual elastic chambers theory. Four hundred clinical trials on real-time non-invasive BG monitoring under suitable experiment conditions were performed on different individuals, including diabetic patients, senior citizens and healthy adults. A multisensory information fusion model was applied to process these samples. The algorithm (we defined it as DCBPN algorithm) applied in the model combines a decision tree and back propagation neural network, which classifies the physiological and environmental parameters into three categories, and then establishes a corresponding prediction model for the three categories. The DCBPN algorithm provides an accuracy of 88.53% in predicting the BG of new samples. Thus, this system demonstrates a great potential to reliably detect BG values in a non-invasive setting.
Yang, Wenming; Liao, Ningfang; Li, Yasheng; Shao, Liwei; Huang, Dehuang
Near infrared (NIR) has prospectively applied in non-invasive blood glucose measurement due to glucose absorption among the 1.0-2.5m spectral bands. However, this significant technology is hard to be developed because of other blood components and low signal-to-noise ratio (SNR). In this work, we presented a non-invasive glucose measurement system using Fourier transform spectrometer which will work in fingertips or other human body tissues. A refrigerated InGaAs detector with high quantum efficiency performing well in the range of 1.0-1.7μm wavelength is used to acquire transmissive radiation. Preliminary experiment investigations were set up to test glucose levels of aqueous solutions with different concentrations. The analytical modeling of the interferogram data is based on arithmetic Fourier transform and supported by the curvilineal characterization. Experimental results show the variation of light intensity among different glucose concentrations and emphasize the obvious absorption of glucose in NIR wave-range. This study confirms the suitability that NIR can be developed in non-invasive glucose measurement.
Saytashev, Ilyas; Glenn, Rachel; Murashova, Gabrielle A.; Osseiran, Sam; Spence, Dana; Evans, Conor L.; Dantus, Marcos
Red blood cells (RBC) in two-photon excited fluorescence (TPEF) microscopy usually appear as dark disks because of their low fluorescent signal. Here we use 15fs 800nm pulses for TPEF, 45fs 1060nm pulses for three-photon excited fluorescence, and third harmonic generation (THG) imaging. We find sufficient fluorescent signal that we attribute to hemoglobin fluorescence after comparing time and wavelength resolved spectra of other expected RBC endogenous fluorophores: NADH, FAD, biliverdin, and bilirubin. We find that both TPEF and THG microscopy can be used to examine erythrocyte morphology non-invasively without breaching a blood storage bag. PMID:27699111
Benes, Jan; Simanova, Alena; Tovarnicka, Tereza; Sevcikova, Silvie; Kletecka, Jakub; Zatloukal, Jan; Pradl, Richard; Chytra, Ivan; Kasal, Eduard
Intermittent blood pressure (BP) monitoring is the standard-of-care during low and intermediate risk anaesthesia, yet it could lead to delayed recognition of BP fluctuations. Perioperative hypotension is known to be associated with postoperative complications. Continuous, non-invasive methods for BP monitoring have been developed recently. We have tested a novel non-invasive, continuous monitor (using the volume clamp method) to assist with maintaining BP in safe ranges for patients undergoing surgery in a beach chair position. Forty adult patients undergoing thyroid gland surgery in an upright position were included in this prospective randomised controlled trial. Patients were equally allocated to the group with continuous monitoring of BP using the CNAP® Monitor and to the control group managed using an intermittent oscillometric BP cuff. The absolute and proportional time spent outside the range of ±20% of the target BP along with other hemodynamic and clinical parameters were evaluated. The continuous monitoring decreased the anaesthesia time spent below -20% pressure range [absolute: 12 min (4-20) vs. 27 min (16-34); p=0.001; relative to procedure length: 14% (7-20) vs. 33.5% (17.5-53); p=0.003]. No significant differences were observed in postoperative morbidity or in hospital length of stay. Continuous non-invasive BP monitoring via the CNAP® Monitor allows for better BP management in patients undergoing surgery in a beach chair position. In our randomised trial the time spent in hypotension was significantly shorter using continuous monitoring.
O'Donoghue, K; Choolani, M; Chan, J; de la Fuente, J; Kumar, S; Campagnoli, C; Bennett, P R; Roberts, I A G; Fisk, N M
Strategies for genetic prenatal diagnosis on fetal cells in the maternal circulation have been limited by lack of a cell type present only in fetal blood. However, the recent identification of mesenchymal stem cells (MSC) in first trimester fetal blood offers the prospect of targeting MSC for non-invasive prenatal diagnosis. We developed protocols for fetal MSC enrichment from maternal blood and determined sensitivity and specificity in mixing experiments of male fetal MSC added to female blood, in dilutions from 1 in 10(5) to 10(8). We then used the optimal protocol to isolate fetal MSC from maternal blood in the first trimester, using blood taken after surgical termination of pregnancy as a model of increased feto-maternal haemorrhage. In model mixtures, we could amplify one male fetal MSC in 2.5 x 10(7) adult female nucleated cells, yielding a 100% pure population of fetal cells, but not one fetal MSC in 10(8) nucleated cells. Fetal MSC were identified in one of 20 post-termination maternal blood samples and confirmed as fetal MSC by XY fluorescence in-situ hybridization (FISH), immunophenotyping and osteogenic and adipogenic differentiation. We report the isolation of fetal MSC from maternal blood; however, their rarity in post-termination blood suggests they are unlikely to have a role in non-invasive prenatal diagnosis. Failure to locate these cells routinely may be attributed to their low frequency in maternal blood, to sensitivity limitations of enrichment technology, and/or to their engraftment in maternal tissues soon after transplacental passage. We speculate that gender microchimerism in post-reproductive maternal tissues might result from feto-maternal trafficking of MSC in early pregnancy.
Li, Li Na; Zhang, Guang Jun; Li, Qing Bo
Blood component non-invasive measurement based on near-infrared (NIR) spectroscopy has become a favorite topic in the field of biomedicine. However, the various noises from instrument measurement and the varying background from absorption of other components (except target analyte) in blood are the main causes, which influenced the prediction accuracy of multivariable calibration. Thinking of backgrounds and noises are always found in high-scale approximation and low-scale detail coefficients. It is possible to identify them by wavelet transform (WT), which has multi-resolution trait and can break spectral signals into different frequency components retaining the same resolution as the original signal. Meanwhile, associating with a criterion of uninformative variable elimination (UVE), it is better to eliminate backgrounds and noises simultaneously and visually. Basic principle and application technology of this pretreatment method, wavelet transform with UVE criterion, were presented in this paper. Three experimental near-infrared spectra data sets, including aqueous solution with four components data sets, plasma data sets, body oral glucose tolerance test (OGTT) data sets, which, including glucose (the target analyte in this study), have all been used in this paper as examples to explain this pretreatment method. The effect of selected wavelength bands in the pretreatment process were discussed, and then the adaptability of different pretreatment method for the uncertainty complex NIR spectra model in blood component non-invasive measurements were also analyzed. This research indicates that the pretreatment methods of wavelet transform with UVE criterion can be used to eliminate varying backgrounds and noises for experimental NIR spectra data directly. Under the spectra area of 1100 to 1700 nm, utilizing this pretreatment method is helpful for us to get a more simple and higher precision multivariable calibration for blood glucose non-invasive measurement
Jiang, Jingying; Zhang, Lingling; Gong, Qiliang; Xu, Kexin
There is a growing body of studies suggesting that NIR spectroscopy is feasible to be used to non-invasive blood glucose sensing. However, previous results reported that blood components are very complicated and in which glucose concentration is relatively low. This feature limited the practical application of NIR spectroscopy to in vivo blood glucose detection. This talk aims to elucidate how the cholesterol influences blood glucose sensing. Spectroscopic measurements show that cholesterol appears the similar absorbance peaks to those of glucose within NIR range. Furthermore, PLS modelling results demonstrate that the measurement concentrations of glucose are on the high side while containing cholesterol. For example, when the cholesterol concentration is 200mg/dl, the measurement result of glucose with near-infrared spectroscopy will increase 7.961882mg/dl comparing to cholesterol-free glucose solution. Therefore, it is necessary to take steps to reduce cholesterol's effects.
Lastovskaia, Elena A.; Gorbunova, Elena V.; Chertov, Aleksandr N.; Korotaev, Valery V.
The relevance of noninvasive method for determining the blood sugar is caused by necessity of regular monitoring of glucose levels in diabetic patients blood. Traditional invasive method is painful, because it requires a finger pricking. Despite the active studies in the field of non-invasive medical diagnostics, to date the painless and inexpensive instrument for blood sugar control for personal use doesn't exist. It's possible to measure the concentration of glucose in the blood with help of spectrophotometry method. It consists of registering and analyzing the spectral characteristics of the radiation which missed, reflected or absorbed by the object. The authors proposed a measuring scheme for studying the spectral characteristics of the radiation, missed by earlobe. Ultra-violet, visible and near infrared spectral ranges are considered. The paper presents the description of construction and working principles of the proposed special retaining clip and results of experiment with real patient.
Pai, Praful P.; Sanki, Pradyut K.; Sarangi, Satyabrata; Banerjee, Swapna
This paper examines the use of photoacoustic spectroscopy (PAS) at an excitation wavelength of 905 nm for making continuous non-invasive blood glucose measurements. The theoretical background of the measurement technique is verified through simulation. An apparatus is fabricated for performing photoacoustic measurements in vitro on glucose solutions and in vivo on human subjects. The amplitude of the photoacoustic signals measured from glucose solutions is observed to increase with the solution concentration, while photoacoustic amplitude obtained from in vivo measurements follows the blood glucose concentration of the subjects, indicating a direct proportionality between the two quantities. A linear calibration method is applied separately on measurements obtained from each individual in order to estimate the blood glucose concentration. The estimated glucose values are compared to reference glucose concentrations measured using a standard glucose meter. A plot of 196 measurement pairs taken over 30 normal subjects on a Clarke error grid gives a point distribution of 82.65% and 17.35% over zones A and B of the grid with a mean absolute relative deviation (MARD) of 11.78% and a mean absolute difference (MAD) of 15.27 mg/dl (0.85 mmol/l). The results obtained are better than or comparable to those obtained using photoacoustic spectroscopy based methods or other non-invasive measurement techniques available. The accuracy levels obtained are also comparable to commercially available continuous glucose monitoring systems.
Zhu, Jianming; Chen, Zhencheng
A non-invasive blood glucose measurement sensor and the data process algorithm based on the metabolic energy conservation (MEC) method are presented in this paper. The physiological parameters of human fingertip can be measured by various sensing modalities, and blood glucose value can be evaluated with the physiological parameters by the multiple linear regression analysis. Five methods such as enter, remove, forward, backward and stepwise in multiple linear regression were compared, and the backward method had the best performance. The best correlation coefficient was 0.876 with the standard error of the estimate 0.534, and the significance was 0.012 (sig. <0.05), which indicated the regression equation was valid. The Clarke error grid analysis was performed to compare the MEC method with the hexokinase method, using 200 data points. The correlation coefficient R was 0.867 and all of the points were located in Zone A and Zone B, which shows the MEC method provides a feasible and valid way for non-invasive blood glucose measurement.
Chen, H; Griffin, D K; Jestice, K; Hackett, G; Cooper, J; Ferguson-Smith, M A
Fetal erythroblasts circulating in maternal blood are important candidate cells for non-invasive prenatal diagnosis. We have cultured erythroblasts from 16 maternal blood samples, both with and without prior enrichment by magnetic activated cell sorting (MACS), in a semi-solid medium containing growth factors. Individual colonies were examined by PCR with sex chromosome-specific primers and microsatellite marker primers. No conclusive Y-chromosome specific amplification could be demonstrated in any of the 16 cases, even when the mother was confirmed to be carrying a male fetus. All colonies tested by microsatellite marker PCR were of maternal origin. Our results suggest that the probability of obtaining fetal colonies from fetal erythroblasts circulating in maternal blood is very low and that approaches for culturing fetal erythroblasts in vitro cannot yet be used reliably for prenatal diagnosis using current methods for fetal cell enrichment.
Wróbel, M. S.
The number of patients with diabetes has reached over 350 million, and still continues to increase. The need for regular blood glucose monitoring sparks the interest in the development of modern detection technologies. One of those methods, which allows for noninvasive measurements, is Raman spectroscopy. The ability of infrared light to penetrate deep into tissues allows for obtaining measurements through the skin without its perforation. This paper presents the limitations and possibilities of non-invasive blood glucose monitoring with Raman spectroscopy. Especially focusing on the possibilities for device miniaturization. Such device incorporates a Raman spectrometer, a fiber-optical probe, and a computing device (microcontroller, smartphone, etc.) which calculates the glucose concentration using specialized algorithms. Simplification of device design, as well as turbidity correction technique and a new proposed method of synchronized detection are described.
Background Altitude and gravity changes during aeromedical evacuations induce exacerbated cardiovascular responses in unstable patients. Non-invasive cardiac output monitoring is difficult to perform in this environment with limited access to the patient. We evaluated the feasibility and accuracy of stroke volume estimation by finger photoplethysmography (SVp) in hypergravity. Methods Finger arterial blood pressure (ABP) waveforms were recorded continuously in ten healthy subjects before, during and after exposure to +Gz accelerations in a human centrifuge. The protocol consisted of a 2-min and 8-min exposure up to +4 Gz. SVp was computed from ABP using Liljestrand, systolic area, and Windkessel algorithms, and compared with reference values measured by echocardiography (SVe) before and after the centrifuge runs. Results The ABP signal could be used in 83.3% of cases. After calibration with echocardiography, SVp changes did not differ from SVe and values were linearly correlated (p<0.001). The three algorithms gave comparable SVp. Reproducibility between SVp and SVe was the best with the systolic area algorithm (limits of agreement −20.5 and +38.3 ml). Conclusions Non-invasive ABP photoplethysmographic monitoring is an interesting technique to estimate relative stroke volume changes in moderate and sustained hypergravity. This method may aid physicians for aeronautic patient monitoring. PMID:25798613
Thomas, Graham H.; Watson, Roger M.; Noell, J. Oakey
A new and improved method and apparatus are provided for non-invasive monitoring of changes in blood glucose concentration in a tissue specimen and particularly in an individual. The method uses acoustic velocity measurements for monitoring the effect of glucose concentration upon the density and adiabatic compressibility of the serum. In a preferred embodiment, the acoustic velocity measurements are made through the earlobe of a subject by means of an acoustic probe or monitor which includes a transducer for transmitting and receiving ultrasonic energy pulses to and from the blood flowing in the subject's earlobe and a reflector for facilitating reflection of the acoustic pulses from the blood. The probe is designed in such a way that when properly affixed to an ear, the transducer is positioned flush against the anterior portion of an earlobe while the reflector is positioned flush against the interior portion of the earlobe. A microthermocouple is provided on the probe for monitoring the internal temperature of the blood being sampled. An electrical system, essentially comprising a frequency generator, a time intervalometer and an oscilloscope, is linked to the glucose monitoring probe. The electrical system analyzes selected ones of the pulses reflected from the blood sample in order to determine therefrom the acoustic velocity of the blood which, in turn, provides a representation of the blood glucose concentration levels at the time of the acoustic velocity measurements.
Min, Xiaolin; Jiang, Jingying; Zou, Da; Liu, Rong; Xu, Kexin
Previous studies have shown the limitations of taking OGTT (Oral Glucose Tolerance Test) as the glucose adjustment protocol for non-invasive blood glucose sensing. Previous studies built a mathematical model of glucose metabolism system-IMM (the Integrated Minimal Model) to probe other available adjustment methods. In this talk, a further study would be focused on more detailed combination options of different glucose input types for glucose adjustment projects in non-invasive blood glucose sensing. And predictive models of blood glucose concentration have been established by means of partial least squares (PLS) method, which could be used to evaluate the quality of different glucose adjustment options. Results of PLS modeling suggested that predictive models under combined glucose input types, compared with OGTT, show a great enhancement in the stability. This would finally improve the precision of non-invasive blood glucose sensing.
Doh, Il; Lim, Hyun Kyoon; Ahn, Bongyoung
Blood pressure is one of the most important vital signs used to monitor a patient’s medical condition and is widely measured in hospitals and at home. Automatic, non-invasive blood pressure (NIBP) monitoring devices measure systolic and diastolic blood pressures from the analysis of cuff pressure oscillations caused by periodic variations of blood pressure in an artery. Currently, clinical validation by comparing them to the auscultatory reference has been used to verify the performance of NIBP devices. However, there are presently no calibration methods for NIBP devices. Here, we propose an SI-traceable calibration method for oscillometric NIBP devices. The calibration system generates pressure-pulses at pre-determined cuff pressures, and with pre-determined amplitude, to the device-under-test. The uncertainty of each pulse is analyzed and used for the calculation of blood pressure (BP) uncertainty. The maximum uncertainty for systolic and diastolic BP using the newly developed calibration system is (0.74 and 0.60) mmHg (k = 2) depending on the pressure and amplitude of each pulse, as well as the number of pulses applied. The present method can be used for calibration of oscillometric NIBP devices.
Petrova, Elena V.; Oraevsky, Alexander A.; Ermilov, Sergey A.
Optoacoustic (photoacoustic) temperature imaging could provide improved spatial resolution and temperature sensitivity as compared to other techniques of non-invasive thermometry used during thermal therapies for safe and efficient treatment of lesions. However, accuracy of the reported optoacoustic methods is compromised by biological variability and heterogeneous composition of tissues. We report our findings on the universal character of the normalized temperature dependent optoacoustic response (ThOR) in blood, which is invariant with respect to hematocrit at the isosbestic point of hemoglobin. The phenomenon is caused by the unique homeostatic compartmentalization of blood hemoglobin exclusively inside erythrocytes. On the contrary, the normalized ThOR in aqueous solutions of hemoglobin showed linear variation with respect to its concentration and was identical to that of blood when extrapolated to the hemoglobin concentration inside erythrocytes. To substantiate the conclusions, we analyzed optoacoustic images acquired from the samples of whole and diluted blood as well as hemoglobin solutions during gradual cooling from +37 to -15 °C. Our experimental methodology allowed direct observation and accurate measurement of the temperature of zero optoacoustic response, manifested as the sample's image faded into background and then reappeared in the reversed (negative) contrast. These findings provide a framework necessary for accurate correlation of measured normalized optoacoustic image intensity and local temperature in vascularized tissues independent of tissue composition.
Petrova, Elena V.; Oraevsky, Alexander A.; Ermilov, Sergey A.
Optoacoustic (photoacoustic) temperature imaging could provide improved spatial resolution and temperature sensitivity as compared to other techniques of non-invasive thermometry used during thermal therapies for safe and efficient treatment of lesions. However, accuracy of the reported optoacoustic methods is compromised by biological variability and heterogeneous composition of tissues. We report our findings on the universal character of the normalized temperature dependent optoacoustic response (ThOR) in blood, which is invariant with respect to hematocrit at the isosbestic point of hemoglobin. The phenomenon is caused by the unique homeostatic compartmentalization of blood hemoglobin exclusively inside erythrocytes. On the contrary, the normalized ThOR in aqueous solutions of hemoglobin showed linear variation with respect to its concentration and was identical to that of blood when extrapolated to the hemoglobin concentration inside erythrocytes. To substantiate the conclusions, we analyzed optoacoustic images acquired from the samples of whole and diluted blood as well as hemoglobin solutions during gradual cooling from +37 to −15 °C. Our experimental methodology allowed direct observation and accurate measurement of the temperature of zero optoacoustic response, manifested as the sample's image faded into background and then reappeared in the reversed (negative) contrast. These findings provide a framework necessary for accurate correlation of measured normalized optoacoustic image intensity and local temperature in vascularized tissues independent of tissue composition. PMID:25316928
Fellner, Claudia; Jung, Ernst M; Prantl, Lukas
Early detection of a compromised circulation of free flaps and an immediate revision may lead to higher rates of flap salvage. The aim of this study was to evaluate the perfusion of the entire flap using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). DCE was performed in 11 patients after flap transplantation using an optimized 3D gradient echo sequence to cover the whole flap. The percentage increase of signal intensity over time was evaluated for the free flap as well as for a reference tissue. Furthermore, normalized signal increase was calculated as the ratio of signal increase within the flaps to the signal increase in the reference tissue. Signal increase in free flaps and reference tissue was compared using the Wilcoxon-test (p < 0.05), normalized signal increase in normally perfused (n = 9) and in flaps with compromised perfusion (n = 2) using Mann-Whitney-test (p < 0.05). Signal increase within normally perfused flaps was similar to the reference tissue. In flaps with compromised perfusion the increase was significantly lower than in reference tissue. Normalized signal increase in adequately perfused flaps and flaps with compromised perfusion also showed a significant difference. DCE MRI may be a valuable non-invasive tool to evaluate tissue perfusion of the complete free flap.
Felipo, Vicente; Urios, Amparo; Giménez-Garzó, Carla; Cauli, Omar; Andrés-Costa, Maria-Jesús; González, Olga; Serra, Miguel A; Sánchez-González, Javier; Aliaga, Roberto; Giner-Durán, Remedios; Belloch, Vicente; Montoliu, Carmina
AIM: To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy. METHODS: Blood flow (BF) was analyzed by arterial spin labeling (ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy (MHE). Images were collected using a 3 Tesla MR scanner (Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE were detected using the battery Psychometric Hepatic Encephalopathy Score (PHES) consisting of five tests. Different cognitive and motor functions were also assessed: alterations in selective attention were evaluated using the Stroop test. Patients and controls also performed visuo-motor and bimanual coordination tests. Several biochemical parameters were measured: serum pro-inflammatory interleukins (IL-6 and IL-18), 3-nitrotyrosine, cGMP and nitrates+nitrites in plasma, and blood ammonia. Bivariate correlations were evaluated. RESULTS: In patients with MHE, BF was increased in cerebellar hemisphere (P = 0.03) and vermis (P = 0.012) and reduced in occipital lobe (P = 0.017). BF in cerebellar hemisphere was also increased in patients without MHE (P = 0.02). Bimanual coordination was impaired in patients without MHE (P = 0.05) and much more in patients with MHE (P < 0.0001). Visuo-motor coordination was impaired only in patients with MHE (P < 0.0001). Attention was slightly affected in patients without MHE and more strongly in patients with MHE (P < 0.0001). BF in cerebellar hemisphere and vermis correlated with performance in most tests of PHES [(number connection tests A (NCT-A), B (NCT-B)and line tracing test] and in the congruent task of Stroop test. BF in frontal lobe correlated with NCT-A. Performance in bimanual and visuomotor coordination tests correlated only with BF in cerebellar hemisphere. BF in occipital lobe correlates with performance in the PHES battery and with
Becker, P.H.; Voigt, C.C.; Arnold, J.M.; Nagel, R.
We describe a non-invasive technique to obtain blood samples from incubating birds without trapping and handling. A larval instar of the blood-sucking bug Dipetalogaster maximus (Heteroptera) was put in a hollowed artificial egg which was placed in a common tern Sterna hirundo) nest. A gauze-covered hole in the egg allowed the bug to draw blood from the brood patch of breeding adults. We successfully collected 68 blood samples of sufficient amount (median=187 ??l). The daily success rate was highest during the early breeding season and averaged 34% for all trials. We could not detect any visible response by the incubating bird to the sting of the bug. This technique allows for non-invasive blood collection from bird species of various sizes without disturbance. ?? Dt. Ornithologen-Gesellschaft e.V. 2005.
Fujiwara, Masaru; Sato, Shun; Abeygunawardhana, Pradeep K. W.; Suzuki, Satoru; Nishiyama, Akira; Wada, Kenji; Ishimaru, Ichiro
To realize the non-invasive blood glucose measurement, it will be effective to acquire the spectroscopic imaging of blood vessels only near the skin surface for eliminating other biological-component's disturbances. Our proposed imaging-type 2-dimensional Fourier spectroscopic imaging can limit the measuring depth into focal plane with high light detection sensitivity. Thus, the proposed method will be suitable for measuring only near the skin surface with detecting weak reflected light from inner biomembrane. But reflectance of skin surface is more than 1000 times larger than inner skin's reflectance. Paying attention on Fresnel reflection, fingers what were illuminated by p-polarized beam from Brewster's angle were observed with crossed-Nicol dark field optics. We successfully acquired spectroscopic characteristics of hemoglobin at vein area near the skin surface.
Jayanthy, A. K.; Sujatha, N.; Reddy, M. Ramasubba; Narayanamoorthy, V. B.
Measuring microcirculatory tissue blood perfusion is of interest for both clinicians and researchers in a wide range of applications and can provide essential information of the progress of treatment of certain diseases which causes either an increased or decreased blood flow. Diabetic ulcer associated with alterations in tissue blood flow is the most common cause of non-traumatic lower extremity amputations. A technique which can detect the onset of ulcer and provide essential information on the progress of the treatment of ulcer would be of great help to the clinicians. A noninvasive, noncontact and whole field laser speckle contrast imaging (LSCI) technique has been described in this paper which is used to assess the changes in blood flow in diabetic ulcer affected areas of the foot. The blood flow assessment at the wound site can provide critical information on the efficiency and progress of the treatment given to the diabetic ulcer subjects. The technique may also potentially fulfill a significant need in diabetic foot ulcer screening and management.
Panerai, R B; Sammons, E L; Smith, S M; Rathbone, W E; Bentley, S; Potter, J F; Samani, N J
Temporal variability of parameters which describe dynamic cerebral autoregulation (CA), usually quantified by the short-term relationship between arterial blood pressure (BP) and cerebral blood flow velocity (CBFV), could result from continuous adjustments in physiological regulatory mechanisms or could be the result of artefacts in methods of measurement, such as the use of non-invasive measurements of BP in the finger. In 27 subjects (61+/-11 years old) undergoing coronary artery angioplasty, BP was continuously recorded at rest with the Finapres device and in the ascending aorta (Millar catheter, BP(AO)), together with bilateral transcranial Doppler ultrasound in the middle cerebral artery, surface ECG and transcutaneous CO(2). Dynamic CA was expressed by the autoregulation index (ARI), ranging from 0 (absence of CA) to 9 (best CA). Time-varying, continuous estimates of ARI (ARI(t)) were obtained with an autoregressive moving-average (ARMA) model applied to a 60 s sliding data window. No significant differences were observed in the accuracy and precision of ARI(t) between estimates derived from the Finapres and BP(AO). Highly significant correlations were obtained between ARI(t) estimates from the right and left middle cerebral artery (MCA) (Finapres r=0.60+/-0.20; BP(AO) r=0.56+/-0.22) and also between the ARI(t) estimates from the Finapres and BP(AO) (right MCA r=0.70+/-0.22; left MCA r=0.74+/-0.22). Surrogate data showed that ARI(t) was highly sensitive to the presence of noise in the CBFV signal, with both the bias and dispersion of estimates increasing for lower values of ARI(t). This effect could explain the sudden drops of ARI(t) to zero as reported previously. Simulated sudden changes in ARI(t) can be detected by the Finapres, but the bias and variability of estimates also increase for lower values of ARI. In summary, the Finapres does not distort time-varying estimates of dynamic CA obtained with a sliding window combined with an ARMA model, but further
Han, Songfeng; Proctor, Ashley R.; Vella, Joseph B.; Benoit, Danielle S. W.; Choe, Regine
Longitudinal blood flow during murine bone graft healing was monitored non-invasively using diffuse correlation tomography. The system utilized spatially dense data from a scanning set-up, non-linear reconstruction, and micro-CT anatomical information. Weekly in vivo measurements were performed. Blood flow changes in autografts, which heal successfully, were localized to graft regions and consistent across mice. Poor healing allografts showed heterogeneous blood flow elevation and high inter-subject variabilities. Allografts with tissue-engineered periosteum showed responses intermediate to both autografts and allografts, consistent with healing observed. These findings suggest that spatiotemporal blood flow changes can be utilized to differentiate the degree of bone graft healing. PMID:27699097
Nogawa, Masamichi; Ogawa, Mitsuhiro; Yamakoshi, Takehiro; Tanaka, Shinobu; Yamakoshi, Ken-ichi
Up to now, we have successfully carried out the non-invasive beat-by-beat measurement of blood pressure (BP) in the root of finger, superficial temporal and radial artery based on the volume-compensation technique with reasonable accuracy. The present study concerns with improvement of control method for this beat-by-beat BP measurement. The measurement system mainly consists of a partial pressurization cuff with a pair of LED and photo-diode for the detection of arterial blood volume, and a digital self-tuning control method. Using healthy subjects, the performance and accuracy of this system were evaluated through comparison experiments with the system using a conventional empirically tuned PID controller. The significant differences of BP measured in finger artery were not showed in systolic (SBP), p=0.52, and diastolic BP (DBP), p=0.35. With the advantage of the adaptive control with self-tuning method, which can tune the control parameters without disturbing the control system, the application area of the non-invasive beat-by-beat measurement method will be broadened.
Han, Guang; Liu, Jin; Liu, Rong; Xu, Kexin
Position-based reference measurement method is taken as one of the most promising method in non-invasive measurement of blood glucose based on spectroscopic methodology. Selecting an appropriate source-detector separation as the reference position is important for deducting the influence of background change and reducing the loss of useful signals. Our group proposed a special source-detector separation named floating-reference position where the signal contains only background change, that is to say, the signal at this source-detector separation is uncorrelated with glucose concentration. The existence of floating-reference position has been verified in a three layer skin by Monte Carlo simulation and in the in vitro experiment. But it is difficult to verify the existence of floating-reference position on the human body because the interference is more complex during in vivo experiment. Aiming at this situation, this paper studies the determination of the best reference position on human body by collecting signals at several source-detector separations on the palm and measuring the true blood glucose levels during oral glucose tolerance test (OGTT) experiments of 3 volunteers. Partial least square (PLS) calibration model is established between the signals at every source-detector separation and its corresponding blood glucose levels. The results shows that the correlation coefficient (R) between 1.32 mm to 1.88 mm is lowest and they can be used as reference for background correction. The signal of this special position is important for improving the accuracy of near-infrared non-invasive blood glucose measurement.
Krivoshei, Andrei; Lamp, Jürgen; Min, Mart; Uuetoa, Tiina; Uuetoa, Hasso; Annus, Paul
The paper presents a method for the Central Aortic Pressure (CAP) waveform estimation from the measured radial Electrical Bio-Impedance (EBI). The method proposed here is a non-invasive and health-safe approach to estimate the cardiovascular system parameters, such as the Augmentation Index (AI). Reconstruction of the CAP curve from the EBI data is provided by spectral domain transfer functions (TF), found on the bases of data analysis. Clinical experiments were carried out on 30 patients in the Center of Cardiology of East-Tallinn Central Hospital during coronary angiography on patients in age of 43 to 80 years. The quality and reliability of the method was tested by comparing the evaluated augmentation indices obtained from the invasively measured CAP data and from the reconstructed curve. The correlation coefficient r = 0.89 was calculated in the range of AICAP values from 5 to 28. Comparing to the traditional tonometry based method, the developed one is more convenient to use and it allows long-term monitoring of the AI, what is not possible with tonometry probes.
Zaproudina, Nina; Teplov, Victor; Nippolainen, Ervin; Lipponen, Jukka A; Kamshilin, Alexei A; Närhi, Matti; Karjalainen, Pasi A; Giniatullin, Rashid
Asymmetrical changes in blood perfusion and asynchronous blood supply to head tissues likely contribute to migraine pathophysiology. Imaging was widely used in order to understand hemodynamic variations in migraine. However, mapping of blood pulsations in the face of migraineurs has not been performed so far. We used the Blood Pulsation Imaging (BPI) technique, which was recently developed in our group, to establish whether 2D-imaging of blood pulsations parameters can reveal new biomarkers of migraine. BPI characteristics were measured in migraineurs during the attack-free interval and compared to healthy subjects with and without a family history of migraine. We found a novel phenomenon of transverse waves of facial blood perfusion in migraineurs in contrast to healthy subjects who showed synchronous blood delivery to both sides of the face. Moreover, the amplitude of blood pulsations was symmetrically distributed over the face of healthy subjects, but asymmetrically in migraineurs and subjects with a family history of migraine. In the migraine patients we found a remarkable correlation between the side of unilateral headache and the direction of the blood perfusion wave. Our data suggest that migraine is associated with lateralization of blood perfusion and asynchronous blood pulsations in the facial area, which could be due to essential dysfunction of the autonomic vascular control in the face. These findings may further enhance our understanding of migraine pathophysiology and suggest new easily available biomarkers of this pathology.
Zaproudina, Nina; Teplov, Victor; Nippolainen, Ervin; Lipponen, Jukka A.; Kamshilin, Alexei A.; Närhi, Matti; Karjalainen, Pasi A.; Giniatullin, Rashid
Asymmetrical changes in blood perfusion and asynchronous blood supply to head tissues likely contribute to migraine pathophysiology. Imaging was widely used in order to understand hemodynamic variations in migraine. However, mapping of blood pulsations in the face of migraineurs has not been performed so far. We used the Blood Pulsation Imaging (BPI) technique, which was recently developed in our group, to establish whether 2D-imaging of blood pulsations parameters can reveal new biomarkers of migraine. BPI characteristics were measured in migraineurs during the attack-free interval and compared to healthy subjects with and without a family history of migraine. We found a novel phenomenon of transverse waves of facial blood perfusion in migraineurs in contrast to healthy subjects who showed synchronous blood delivery to both sides of the face. Moreover, the amplitude of blood pulsations was symmetrically distributed over the face of healthy subjects, but asymmetrically in migraineurs and subjects with a family history of migraine. In the migraine patients we found a remarkable correlation between the side of unilateral headache and the direction of the blood perfusion wave. Our data suggest that migraine is associated with lateralization of blood perfusion and asynchronous blood pulsations in the facial area, which could be due to essential dysfunction of the autonomic vascular control in the face. These findings may further enhance our understanding of migraine pathophysiology and suggest new easily available biomarkers of this pathology. PMID:24324592
Han, Songfeng; Hoffman, Michael D.; Proctor, Ashley R.; Vella, Joseph B.; Mannoh, Emmanuel A.; Barber, Nathaniel E.; Kim, Hyun Jin; Jung, Ki Won; Benoit, Danielle S. W.; Choe, Regine
Vascular infiltration and associated alterations in microvascular blood flow are critical for complete bone graft healing. Therefore, real-time, longitudinal measurement of blood flow has the potential to successfully predict graft healing outcomes. Herein, we non-invasively measure longitudinal blood flow changes in bone autografts and allografts using diffuse correlation spectroscopy in a murine femoral segmental defect model. Blood flow was measured at several positions proximal and distal to the graft site before implantation and every week post-implantation for a total of 9 weeks (autograft n = 7 and allograft n = 10). Measurements of the ipsilateral leg with the graft were compared with those of the intact contralateral control leg. Both autografts and allografts exhibited an initial increase in blood flow followed by a gradual return to baseline levels. Blood flow elevation lasted up to 2 weeks in autografts, but this duration varied from 2 to 6 weeks in allografts depending on the spatial location of the measurement. Intact contralateral control leg blood flow remained at baseline levels throughout the 9 weeks in the autograft group; however, in the allograft group, blood flow followed a similar trend to the graft leg. Blood flow difference between the graft and contralateral legs (ΔrBF), a parameter defined to estimate graft-specific changes, was elevated at 1–2 weeks for the autograft group, and at 2–4 weeks for the allograft group at the proximal and the central locations. However, distal to the graft, the allograft group exhibited significantly greater ΔrBF than the autograft group at 3 weeks post-surgery (p < 0.05). These spatial and temporal differences in blood flow supports established trends of delayed healing in allografts versus autografts. PMID:26625352
Han, Songfeng; Hoffman, Michael D; Proctor, Ashley R; Vella, Joseph B; Mannoh, Emmanuel A; Barber, Nathaniel E; Kim, Hyun Jin; Jung, Ki Won; Benoit, Danielle S W; Choe, Regine
Vascular infiltration and associated alterations in microvascular blood flow are critical for complete bone graft healing. Therefore, real-time, longitudinal measurement of blood flow has the potential to successfully predict graft healing outcomes. Herein, we non-invasively measure longitudinal blood flow changes in bone autografts and allografts using diffuse correlation spectroscopy in a murine femoral segmental defect model. Blood flow was measured at several positions proximal and distal to the graft site before implantation and every week post-implantation for a total of 9 weeks (autograft n = 7 and allograft n = 10). Measurements of the ipsilateral leg with the graft were compared with those of the intact contralateral control leg. Both autografts and allografts exhibited an initial increase in blood flow followed by a gradual return to baseline levels. Blood flow elevation lasted up to 2 weeks in autografts, but this duration varied from 2 to 6 weeks in allografts depending on the spatial location of the measurement. Intact contralateral control leg blood flow remained at baseline levels throughout the 9 weeks in the autograft group; however, in the allograft group, blood flow followed a similar trend to the graft leg. Blood flow difference between the graft and contralateral legs (ΔrBF), a parameter defined to estimate graft-specific changes, was elevated at 1-2 weeks for the autograft group, and at 2-4 weeks for the allograft group at the proximal and the central locations. However, distal to the graft, the allograft group exhibited significantly greater ΔrBF than the autograft group at 3 weeks post-surgery (p < 0.05). These spatial and temporal differences in blood flow supports established trends of delayed healing in allografts versus autografts.
Stepień, Mariusz; Banach, Maciej; Jankowski, Piotr; Rysz, Jacek
Central arterial systolic blood pressure is a very important factor in the pathophysiology of cardiovascular diseases. Central arterial pressure is a better predictor of cardiovascular risk than peripheral brachial blood pressure. Measurement of central blood pressure is useful for a diagnosis of spurious systolic hypertension in young people. Antihypertensive drugs have a different impact on central blood pressure, for example angiotensin converting enzyme inhibitors, antagonists of angiotensin II receptors, calcium channel blockers more effectively lower central blood pressure than betablockers, despite all of those drugs (including beta-blockers) having a similar impact on peripheral pressure. This mechanism may be responsible for the beneficial effect of some antihypertensive drugs on cardiovascular end points observed in clinical trials, despite a low peripheral hypotensive effect. However, further clinical trials are required to provide more evidence for the prognostic and therapeutic implications of the measurement of central blood pressure before adopting its routine application in clinical practice.
Tang, Hong; Zhang, Jinghui; Chen, Huaming; Mondal, Ashok; Park, Yongwan
Heart sounds (HSs) are produced by the interaction of the heart valves, great vessels, and heart wall with blood flow. Previous researchers have demonstrated that blood pressure can be predicted by exploring the features of cardiac sounds. These features include the amplitude of the HSs, the ratio of the amplitude, the systolic time interval, and the spectrum of the HSs. A single feature or combinations of several features have been used for prediction of blood pressure with moderate accuracy. Experiments were conducted with three beagles under various levels of blood pressure induced by different doses of epinephrine. The HSs, blood pressure in the left ventricle and electrocardiograph signals were simultaneously recorded. A total of 31 records (18 262 cardiac beats) were collected. In this paper, 91 features in various domains are extracted and their linear correlations with the measured blood pressures are examined. These features are divided into four groups and applied individually at the input of a neural network to predict the left ventricular blood pressure (LVBP). The analysis shows that non-spectral features can track changes of the LVBP with lower standard deviation. Consequently, the non-spectral feature set gives the best prediction accuracy. The average correlation coefficient between the measured and the predicted blood pressure is 0.92 and the mean absolute error is 6.86 mmHg, even when the systolic blood pressure varies in the large range from 90 mmHg to 282 mmHg. Hence, systolic blood pressure can be accurately predicted even when using fewer HS features. This technique can be used as an alternative to real-time blood pressure monitoring and it has promising applications in home health care environments.
Lin, Chung-Yin; Hsieh, Han-Yi; Pitt, William G; Huang, Chiung-Yin; Tseng, I-Chou; Yeh, Chih-Kuang; Wei, Kuo-Chen; Liu, Hao-Li
Focused ultrasound (FUS) exposure in the presence of microbubbles can temporally open the blood-brain barrier (BBB) and is an emerging technique for non-invasive brain therapeutic agent delivery. Given the potential to deliver large molecules into the CNS via this technique, we propose a reliable strategy to synergistically apply FUS-BBB opening for the non-invasive and targeted delivery of non-viral genes into the CNS for therapeutic purpose. In this study, we developed a gene-liposome system, in which the liposomes are designed to carry plasmid DNA (pDNA, containing luciferase reporter gene) to form a liposomal-plasmid DNA (LpDNA) complex. Pulsed FUS exposure was delivered to induce BBB opening (500-kHz, burst length=10ms, 1% duty cycle, PRF=1Hz). The longitudinal expression of luciferase was quantitated via an in vivo imaging system (IVIS). The reporter gene expression level was confirmed via immunoblotting, and histological staining was used to identify transfected cells via fluorescent microscopy. In a comparison of gene transduction efficiency, the LpDNA system showed better cell transduction than the pDNA system. With longitudinal observation of IVIS monitoring, animals with FUS treatment showed significant promotion of LpDNA release into the CNS and demonstrated enhanced expression of genes upon sonication with FUS-BBB opening, while both the luciferase and GDNF protein expression were successfully measured via Western blotting. The gene expression peak was observed at day 2, and the gene expression level was up to 5-fold higher than that in the untreated hemisphere (compared to a 1-fold increase in the direct-inject positive-control group). The transfection efficiency was also found to be LpDNA dose-dependent, where higher payloads of pDNA resulted in a higher transfection rate. Immunoblotting and histological staining confirmed the expression of reporter genes in glial cells as well as astrocytes. This study suggests that IV administration of LpDNA in
Nguyen, D.; Nguyen, Hienvu; Roveda, Janet
In this paper, we present a design of a multi optical modalities blood glucose monitor. The Monte Carlo tissues optics simulation with typical human skin model suggests the SNR ratio for a detector sensor is 104 with high sensitivity that can detect low blood sugar limit at 1 mMole/dL ( <20 mg/dL). A Bayesian filtering algorithm is proposed for multisensor fusion to identify whether e user has the danger of having diabetes. The new design has real time response (on the average of 2 minutes) and provides great potential to perform real time monitoring for blood glucose.
Lötsch, Jörn; Skarke, Carsten; Darimont, Jutta; Zimmermann, Michael; Bräutigam, Lutz; Geisslinger, Gerd; Ultsch, Alfred; Oertel, Bruno G
Surrogates may provide easy and quick access to information about pharmacological parameters of interest that can be directly measured only with difficulty. Surrogates have been proposed for opioid blood concentrations to replace invasive sampling, serving as a basis for target-controlled infusion systems to optimize analgesia. We aimed at identifying surrogates of remifentanil steady-state blood concentrations with relevance for its clinical, in particular, analgesic, effects. A "single ascending dose" study design assessed concentration-dependent effects of remifentanil in a double-blind randomized fashion in 16 healthy volunteers. Remifentanil was administered by means of computerized infusion aimed at steady-state effect-site concentrations of 0, 1.2, 1.8, 2.4, 3, 3.6, 4.8, and 6 ng/ml (one concentration per subject, two subjects per concentration). Arterial remifentanil blood concentrations were measured during apparent steady state. Pharmacodynamic parameters were measured at baseline and during steady-state conditions. Potential surrogate parameters included the pupil diameter, the amplitude of pupil light reflex, and the performance in a visual tracking task. Clinical parameters were analgesia to experimental pain, nausea, tiredness, and visual acuity. Remifentanil blood concentrations were well predicted by its effects on the pupil light reflex amplitude, better than by its miotic effects. However, the best prediction for both remifentanil blood concentrations and analgesic effects was obtained using a combination of three surrogate parameters (pupil diameter, light reflex amplitude, and tracking performance). This combination of pharmacodynamic parameters provided even better predictions of analgesia than could be obtained using the measured opioid blood concentrations. Developing surrogates only for opioid blood concentrations is insufficient when opioid effects are the final goal. Combining pharmacodynamic surrogate parameters seems to provide a
NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Adkins, AL, Moran, AV 5d. PROJECT NUMBER 5e. TASK NUMBER 6.2 5f. WORK UNIT ...technicians. The toenail clip method provided an easily trained, easily performed method of blood collection that yielded up to one milliliter of blood...collection, toenail clips, toenail bleeds 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF
Jiang, Jingying; Min, Xiaolin; Zou, Da; Xu, Kexin
Currently, blood glucose concentration levels from OGTT(Oral Glucose Tolerance Test) results are used to build PLS model in noninvasive blood glucose sensing by Near-Infrared(NIR) Spectroscopy. However, the univocal dynamic change trend of blood glucose concentration based on OGTT results is not various enough to provide comprehensive data to make PLS model robust and accurate. In this talk, with the final purpose of improving the stability and accuracy of the PLS model, we introduced an integrated minimal model(IMM) of glucose metabolism system. First, by adjusting parameters, which represent different metabolism characteristics and individual differences, comparatively ideal mediation programs to different groups of people, even individuals were customized. Second, with different glucose input types(oral method, intravenous injection, or intravenous drip), we got various changes of blood glucose concentration. And by studying the adjustment methods of blood glucose concentration, we would thus customize corresponding experimental protocols of glucose adjustment to different people for noninvasive blood glucose concentration and supply comprehensive data for PLS model.
Alomari, A H; Savkin, A V; Ayre, P J; Lim, E; Mason, D G; Salamonsen, R F; Fraser, J F; Lovell, N H
We propose a dynamical model for mean inlet pressure estimation in an implantable rotary blood pump during the diastolic period. Non-invasive measurements of pump impeller rotational speed (ω), motor power (P), and pulse width modulation signal acquired from the pump controller were used as inputs to the model. The model was validated over a wide range of speed ramp studies, including (i) healthy (C1), variations in (ii) heart contractility (C2); (iii) afterload (C2, C3, C4), and (iv) preload (C5, C6, C7). Linear regression analysis between estimated and extracted mean inlet pressure obtained from in vivo animal data (greyhound dogs, N = 3) resulted in a highly significant correlation coefficients (R(2) = 0.957, 0.961, 0.958, 0.963, 0.940, 0.946, and 0.959) and mean absolute errors of (e = 1.604, 2.688, 3.667, 3.990, 2.791, 3.215, and 3.225 mmHg) during C1, C2, C3, C4, C5, C6, and C7, respectively. The proposed model was also used to design a controller to regulate mean diastolic pump inlet pressure using non-invasively measured ω and P. In the presence of model uncertainty, the controller was able to track and settle to the desired input within a finite number of sampling periods and minimal error (0.92 mmHg). The model developed herein will play a crucial role in developing a robust control system of the pump that detects and thus avoids undesired pumping states by regulating the inlet pressure within a predefined physiologically realistic limit.
Sullivan, C S; Casaburi, R; Storer, T W; Wasserman, K
We determined the ability of gas exchange analyses during incremental exercise tests (IXT) to predict blood lactate levels associated with a range of constant power output cycle ergometer tests. Twenty-seven healthy young men performed duplicate IXT and four 15-min constant power output tests at intensities ranging from moderate to very severe, before and after a training program. End-exercise blood lactate levels were approximated from superficial venous samples obtained 60 s after each constant power output test. From IXT, the power outputs corresponding to peak oxygen uptake (Wmax) and lactic acidosis threshold (WLAT), were determined. We examined the ability of four measures of exercise intensity to predict blood lactate levels for power outputs above the LAT: (1) power output (W), (2) power difference (W-WLAT), (3) power fraction (W/Wmax) and (4) power difference to delta ratio [(W-WLAT)/(Wmax-WLAT)]. Correlation coefficients were r = 0.38, 0.69, 0.75, and 0.81, respectively. The best linear regression prediction equation was: lactate (mmol.l-1) = 12.2[(W-WLAT)/(Wmax-WLAT)] + 0.7 mmol.l-1. This relationship was not significantly affected by training, despite increased values of LAT and peak oxygen uptake. Normalizing exercise intensity to the range of power outputs between WLAT and Wmax provided an estimate of blood lactate response to constant power outputs with a standard error of the estimate of 1.66 mmol.l-1.
Seyed Jafari, S Morteza; Schawkat, Megir; Van De Ville, Dimitri; Shafighi, Maziar
We used real-time LDI to study regional variations in microcirculatory perfusion in healthy candidates to establish a new methodology for global perfusion body mapping that is based on intra-individual perfusion index ratios. Our study included 74 (37 female) healthy volunteers aged between 22 and 30 years (mean 24.49). Imaging was performed using a recent microcirculation-imaging camera (EasyLDI) for different body regions of each volunteer. The perfusion values were reported in Arbitrary Perfusion Units (APU). The relative perfusion indexes for each candidate's body region were then obtained by normalization with the perfusion value of the forehead. Basic parameters such as weight, height, and blood pressure were also measured and analyzed. The highest mean perfusion value was reported in the forehead area (259.21APU). Mean perfusion in the measured parts of the body correlated positively with mean forehead value, while there was no significant correlation between forehead blood perfusion values and room temperature, BMI, systolic blood pressure and diastolic blood pressure (p=0.420, 0.623, 0.488, 0.099, respectively). Analysis of the data showed that perfusion indexes were not significantly different between male and female volunteers except for the ventral upper arm area (p=.001). LDI is a non-invasive, fast technique that opens several avenues for clinical applications. The mean perfusion indexes are useful in clinical practice for monitoring patients before and after surgical interventions. Perfusion values can be predicted for different body parts for patients only by taking the forehead perfusion value and using the perfusion index ratios to obtain expected normative perfusion values.
Sesarini, Carla; Argibay, Pablo; Otaño, Lucas
Current prenatal diagnosis of monogeneic and chromosomal diseases, includes invasive procedures which carry a small but significant risk. For many years, analysis of fetal cells in maternal circulation has been studied, however it has failed its clinical use due to the scarcity of these cells and their persistance after delivery. For more than a decade, the presence of cell-free fetal DNA in maternal blood has been identified. These fetal DNA fragments would derive from the placenta and are not detected after delivery, making them a source of fetal material for carrying out diagnosis techniques using maternal blood. However, the vast majority of cell free DNA in maternal circulation is of maternal origin, with the fetal component contributing from 3% to 6% and rising towards term. Available methodologies do not allow separation of fetal from maternal cell free DNA, so current applications have been focused on the analysis of genes not present in the mother, such as Y chromosome sequences, or RHD gene in RhD-negative women, or paternal or de novo mutations. Also, the detection of cell-free fetal RNA in maternal blood offers the possibility of obtaining information regarding genetic expression profiles of embrionic tissues, and using genes expressed only at the feto-placental unit, controls for the presence of fetal material could be established, regardless of maternal genetic tissue. The present article describes the evidences regarding the passage of fetal nucleic acids to maternal circulation, its current prenatal diagnosis application and possible future perspectives.
Siravegna, Giulia; Bardelli, Alberto
Most solid tumors, including colorectal cancers, shed cell-free DNA (ctDNA) in the blood. ctDNA can be analyzed to generate molecular profiles which capture the heterogeneity of the disease more comprehensively then tumor tissue biopsies. This approach commonly called 'liquid biopsy' can be applied to monitor response to therapy, to assess minimal residual disease and to uncover the emergence of drug resistance. This review will discuss current and future developments of ctDNA analysis in the clinical management of colorectal cancer patients.
Lysenko, S. A.; Kugeiko, M. M.
A statistical ensemble of structural and biophysical parameters of neonatal skin was modeled based on experimental data. Diffuse scattering coefficients of the skin in the visible and infrared regions were calculated by applying a Monte-Carlo method to each realization of the ensemble. The potential accuracy of recovering the bilirubin concentration in dermis (which correlates closely with that in blood) was estimated from spatially resolved spectrometric measurements of diffuse scattering. The possibility to determine noninvasively the bilirubin concentration was shown by measurements of diffuse scattering at λ = 460, 500, and 660 nm at three source-detector separations under conditions of total variability of the skin biophysical parameters.
Voigt, Christian C; Helversen, Otto Von; Michener, Robert H; Kunz, Thomas H
Two techniques for bleeding small mammals have been used in doubly-labeled water (DLW) studies, including vena puncture and the use of starved nymphal stages of hematophagous reduviid bugs (Reduviidae, Hemiptera). In this study, we tested the validity of using reduviid bugs in doubly-labeled water experiments. We found that the isotope enrichment in initial blood samples collected with bugs was significantly lower compared to isotope enrichment in blood samples obtained using vena puncture. We therefore used the desiccation method for estimating total body water (TBW) in DLW experiments because TBW calculated using the isotope dilution method was overestimated when blood samples were collected using reduviid bugs. In our validation experiment with nectar-feeding bats (Glossophaga soricina), we compared estimates of daily energy expenditure (DEE) using DLW with those derived from the energy balance method. We considered Speakman's equation (controlling for 25% fractionated water loss) as the most appropriate for our study animal and calculated DEE accordingly. On average, DEE estimated with DLW was not significantly different from the mean value obtained with the energy balance method (mean deviation 1.2%). We conclude that although bug hemolymph or intestinal liquids most likely contaminate the samples, estimates of DEE are still valid because the DLW method does not depend on absolute isotope enrichments but on the rate of isotope decrease over time. However, dilution of blood with intestinal liquids or hemolymph from a bug may lead to larger variation in DEE estimates. We also tested how the relative error of DLW estimates changed with varying assumptions about fractionation. We used three additional equations for calculating DEE in DLW experiments. The basic equation for DLW experiments published by Lifson and McClintock (LM-6) assumes no fractionation, resulted in an overestimate of DEE by 10%. Nagy's equation (N-2) controls for changes in body mass but not for
Eslami, Parastou; Seo, Jung-Hee; Rahsepar, Amirali; George, Richard; Lardo, Albert; Mittal, Rajat
Coronary computed tomography angiography (CTA) is a promising tool for assessment of coronary stenosis and plaque burden. Recent studies have shown the presence of axial contrast concentration gradients in obstructed arteries, but the mechanism responsible for this phenomenon is not well understood. We use computational fluid dynamics to study intracoronary contrast dispersion and the correlation of concentration gradients with intracoronary blood flow and stenotic severity. Data from our CFD patient-specific simulations reveals that contrast dispersions are generated by intracoronary advection effects, and therefore, encode the coronary flow velocity. This novel method- Transluminal Attenuation Flow Encoding (TAFE) - is used to estimate the flowrate in phantom studies as well as preclinical experiments. Our results indicate a strong correlation between the values estimated from TAFE and the values measured in these experiments. The flow physics of contrast dispersion associated with TAFE will be discussed. This work is funded by grants from Coulter Foundation and Maryland Innovation Initiative. The authors have pending patents in this technology and RM and ACL have other financial interests associated with TAFE.
Mietsch, M; Einspanier, A
The common marmoset (Callithrix jacchus, C. j.) is an established primate model in biomedical research and for human-related diseases. Monitoring of cardiovascular parameters including blood pressure (BP) is important for the health surveillance of these experimental animals and the quantification of diseases or pharmaceutical substances influencing BP. Measurement guidelines for C. j. do not exist yet; therefore, the present study was carried out to establish a practicable protocol based on recommendations of the American College of Veterinary Internal Medicine (ACVIM). Furthermore, BP data of 49 marmosets (13.8-202.4 months of age) were obtained via high-definition oscillometry to further knowledge of physiological parameters and gender-related differences in this primate. The thighs proved to be the most suitable measurement localization, since systolic values were less variable (left 4.03 ± 2.90%, right 5.96 ± 2.77%) compared with the tail (12.7 ± 6.96%). BP values were similar in the morning and in the afternoon (P > 0.05). Data were highly reproducible within and between several sessions on three consecutive days (P > 0.05) as well as over the course of 20 months (P > 0.05). Furthermore, the measurement time for females was significantly shorter than for males (5:14 ± 1:59 min versus 6:50 ± 1:58 min, P = 0.007). Measurement recommendations for the common marmoset were successfully established. Standardized values enabled a reliable comparison of BP parameters, e.g. for cardiovascular, toxicological or metabolic research.
Perlado-Marina, Sara; Bustamante-Aragones, Ana; Horcajada, Laura; Trujillo-Tiebas, Maria Jose; Lorda-Sanchez, Isabel; Ruiz Ramos, Marta; Plaza, Javier; Rodriguez de Alba, Marta
Since the discovery of the presence of fetal DNA in maternal blood, non-invasive fetal sex determination has been the test most widely translated into clinical practice. To date there is no agreement between the different laboratories performing such tests in relation to which is the best protocol. As a consequence there are almost as many protocols as laboratories offering the service, using different methodologies and thus obtaining different diagnostic accuracies. By the end of 2007, after a validation study performed in 316 maternal samples collected between the 5th and 12th week of gestation, the fetal sex determination was incorporated into clinical practice in our Service. The test is performed in the first trimester of pregnancy, and it is offered as part of the genetic counseling process for couples at risk of X-linked disorders. As a general rule and in order to avoid misdiagnosis, two samples at different gestational ages are tested per patient. The analysis is performed by the study of the SRY gene by RT-PCR. Two hundred and twenty six pregnancies have been tested so far in these 5 years. Neither false positives nor false negatives diagnoses have been registered, thus giving a diagnostic accuracy of 100%. PMID:26835681
Xiang, Yuqian; Zhang, Junyu; Li, Qiaoli; Zhou, Xinyao; Wang, Teng; Xu, Mingqing; Xia, Shihui; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi
Utilizing epigenetic (DNA methylation) differences to differentiate between maternal peripheral blood (PBL) and fetal (placental) DNA has been a promising strategy for non-invasive prenatal testing (NIPT). However, the differentially methylated regions (DMRs) have yet to be fully ascertained. In the present study, we performed genome-wide comparative methylome analysis between maternal PBL and placental DNA from pregnancies of first trimester by methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) and Infinium HumanMethylation450 BeadChip assays. A total of 36 931 DMRs and 45 804 differentially methylated sites (DMSs) covering the whole genome, exclusive of the Y chromosome, were identified via MeDIP-Seq and Infinium 450k array, respectively, of which 3759 sites in 2188 regions were confirmed by both methods. Not only did we find the previously reported potential fetal DNA markers in our identified DMRs/DMSs but also we verified fully the identified DMRs/DMSs in the validation round by MassARRAY EpiTYPER. The screened potential fetal DNA markers may be used for NIPT on aneuploidies and other chromosomal diseases, such as cri du chat syndrome and velo-cardio-facial syndrome. In addition, these potential markers may have application in the early diagnosis of placental dysfunction, such as pre-eclampsia.
Wang, Xian-ju; Zeng, Chang-chun; Liu, Han-ping; Liu, Song-hao; Liu, Liang-gang
Based on Pennes equation, the influences of the intensity and the impulse frequency of laser acupuncture on the point tissues' blood flow perfusion rate are discussed. We find that the blood perfusion rate of point tissue increases with the intensity of laser acupuncture increasing. After impulse laser acupuncture the point tissue blood perfusion rate increase little, but after continuum laser acupuncture the point tissues blood perfusion rate increase much.
Harju, Jarkko; Vehkaoja, Antti; Kumpulainen, Pekka; Campadello, Stefano; Lindroos, Ville; Yli-Hankala, Arvi; Oksala, Niku
Intermittent non-invasive blood pressure measurement with tourniquets is slow, can cause nerve and skin damage, and interferes with other measurements. Invasive measurement cannot be safely used in all conditions. Modified arterial tonometry may be an alternative for fast and continuous measurement. Our aim was to compare arterial tonometry sensor (BPro(®)) with invasive blood pressure measurement to clarify whether it could be utilized in the postoperative setting. 28 patients who underwent elective surgery requiring arterial cannulation were analyzed. Patients were monitored post-operatively for 2 h with standard invasive monitoring and with a study device comprising an arterial tonometry sensor (BPro(®)) added with a three-dimensional accelerometer to investigate the potential impact of movement. Recordings were collected electronically. The results revealed inaccurate readings in method comparison between the devices based on recommendations by Association for the Advancement of Medical Instrumentation (AAMI). On a Bland-Altman plot, the bias and precision between these two methods was 19.8 ± 16.7 (Limits of agreement - 20.1 to 59.6) mmHg, Spearman correlation coefficient r = 0.61. For diastolic pressure, the difference was 4.8 ± 7.7 (LoA - 14.1 to 23.6) mmHg (r = 0.72), and for mean arterial pressure it was 11.18 ± 11.1 (LoA - 12.1 to 34.2) mmHg (r = 0.642). Our study revealed inaccurate agreement (AAMI) between the two methods when measuring systolic and mean blood pressures during post-operative care. The readings for diastolic pressures were inside the limits recommended by AAMI. Movement increased the failure rate significantly (p < 0.001). Thus, arterial tonometry is not an appropriate replacement for invasive blood pressure measurement in these patients.
Iakovlev, Dmitry; Dwyer, Vincent; Hu, Sijung; Silberschmidt, Vadim
Non-contact imaging photoplethysmography (iPPG) to detect pulsatile blood microcirculation in tissue has been selected as a successor to low spatial resolution and slow scanning blood perfusion techniques currently employed by clinicians. The proposed iPPG system employs a novel illumination source constructed of multiple high power LEDs with narrow spectral emission, which are temporally modulated and synchronised with a high performance sCMOS sensor. To ensure spectrum stability and prevent thermal wavelength drift due to junction temperature variations, each LED features a custom-designed thermal management system to effectively dissipate generated heat and auto-adjust current flow. The use of a multi-wavelength approach has resulted in simultaneous microvascular perfusion monitoring at various tissue depths, which is an added benefit for specific clinical applications. A synchronous detection algorithm to extract weak photoplethysmographic pulse-waveforms demonstrated robustness and high efficiency when applied to even small regions of 5 mm2. The experimental results showed evidences that the proposed system could achieve noticeable accuracy in blood perfusion monitoring by creating complex amplitude and phase maps for the tissue under examination.
Delles, Michael; Rengier, Fabian; Azad, Yoo-Jin; Bodenstedt, Sebastian; von Tengg-Kobligk, Hendrik; Ley, Sebastian; Unterhinninghofen, Roland; Kauczor, Hans-Ulrich; Dillmann, Rüdiger
In diagnostics and therapy control of cardiovascular diseases, detailed knowledge about the patient-specific behavior of blood flow and pressure can be essential. The only method capable of measuring complete time-resolved three-dimensional vector fields of the blood flow velocities is velocity-encoded magnetic resonance imaging (MRI), often denoted as 4D flow MRI. Furthermore, relative pressure maps can be computed from this data source, as presented by different groups in recent years. Hence, analysis of blood flow and pressure using 4D flow MRI can be a valuable technique in management of cardiovascular diseases. In order to perform these tasks, all necessary steps in the corresponding process chain can be carried out in our in-house developed software framework MEDIFRAME. In this article, we apply MEDIFRAME for a study of hemodynamics in the pulmonary arteries of five healthy volunteers. The study included measuring vector fields of blood flow velocities by phase-contrast MRI and subsequently computing relative blood pressure maps. We visualized blood flow by streamline depictions and computed characteristic values for the left and the right pulmonary artery (LPA and RPA). In all volunteers, we observed a lower amount of blood flow in the LPA compared to the RPA. Furthermore, we visualized blood pressure maps using volume rendering and generated graphs of pressure differences between the LPA, the RPA and the main pulmonary artery. In most volunteers, blood pressure was increased near to the bifurcation and in the proximal LPA, leading to higher average pressure values in the LPA compared to the RPA.
OBrien, Timothy J; Roghani, Ali R; Jones, Philip A; Aardema, Charles H; Robertson, John L; Diller, Thomas E
A new thin-filmed perfusion sensor was developed using a heat flux gauge, thin-film thermocouple, and a heating element. This sensor, termed "CHFT+", is an enhancement of the previously established CHFT (combined heat flux - temperature) sensor technology predominately used to quantify the severity of burns . The CHFT+ sensor was uniquely designed to measure tissue perfusion on explanted organs destined for transplantation, but could be functionalized and used in a wide variety of other biomedical applications. Exploiting the thin and semi-flexible nature of the new CHFT+ sensor assembly, perfusion measurements can be made from the underside of the organ - providing a quantitative, indirect measure of capillary pressure occlusion. Results from a live tissue test demonstrated, for the first time, the effects of pressure occlusion on an explanted porcine kidney. CHFT+ sensors were placed on top of and underneath 18 kidneys to measure and compare perfusion at perfusate temperatures of 5˚C and 20˚C. The data collected shows greater perfusion on the topside than the underside of the specimen for the length of the experiment. This indicates that pressure occlusion is truly affecting the perfusion and thus, the overall preservation of explanted organs. Moreover, the results demonstrate the effect of preservation temperature on the tissue vasculature. Focusing on the topside perfusion only, the 20˚C perfusion was greater than the 5˚C perfusion, likely due to the vasoconstrictive response at the lower perfusion temperatures.
Front, D.; Groshar, D.; Israel, O.; Robinson, E.
Perfusion blood pool mismatch using Tc-99m labeled red blood cells (RBCs) in a hemangioma of the tongue is described. The method is useful in the evaluation of size of the residual blood pool after irradiation of the tumor.
Baranyi, Andreas; Amouzadeh-Ghadikolai, Omid; Lewinski, Dirk von; Breitenecker, Robert J.; Stojakovic, Tatjana; März, Winfried; Robier, Christoph; Rothenhäusler, Hans-Bernd; Mangge, Harald; Meinitzer, Andreas
Quinolinic acid, a macrophage/microglia-derived excitotoxin fulfills a plethora of functions such as neurotoxin, gliotoxin, and proinflammatory mediator, and it alters the integrity and cohesion of the blood-brain barrier in several pathophysiological states. Beta-trace protein (BTP), a monomeric glycoprotein, is known to indicate cerebrospinal fluid leakage. Thus, the prior aim of this study was to investigate whether BTP might non-invasively indicate quinolinic acid-induced impaired blood-brain barrier integrity. The research hypotheses were tested in three subsamples with different states of immune activation (patients with HCV-infection and interferon-α, patients with major depression, and healthy controls). BTP has also been described as a sensitive marker in detecting impaired renal function. Thus, the renal function has been considered. Our study results revealed highest quinolinic acid and highest BTP- levels in the subsample of patients with HCV in comparison with the other subsamples with lower or no immune activation (quinolinic acid: F = 21.027, p < 0.001 [ANOVA]; BTP: F = 6.792, p < 0.01 [ANOVA]). In addition, a two-step hierarchical linear regression model showed that significant predictors of BTP levels are quinolinic acid, glomerular filtration rate and age. The neurotoxin quinolinic acid may impair blood-brain barrier integrity. BTP might be a new non-invasive biomarker to indicate quinolinic acid-induced impaired blood-brain barrier integrity. PMID:28276430
Rybynok, V. O.; Kyriacou, P. A.
Diabetes is one of the biggest health challenges of the 21st century. The obesity epidemic, sedentary lifestyles and an ageing population mean prevalence of the condition is currently doubling every generation. Diabetes is associated with serious chronic ill health, disability and premature mortality. Long-term complications including heart disease, stroke, blindness, kidney disease and amputations, make the greatest contribution to the costs of diabetes care. Many of these long-term effects could be avoided with earlier, more effective monitoring and treatment. Currently, blood glucose can only be monitored through the use of invasive techniques. To date there is no widely accepted and readily available non-invasive monitoring technique to measure blood glucose despite the many attempts. This paper challenges one of the most difficult non-invasive monitoring techniques, that of blood glucose, and proposes a new novel approach that will enable the accurate, and calibration free estimation of glucose concentration in blood. This approach is based on spectroscopic techniques and a new adaptive modelling scheme. The theoretical implementation and the effectiveness of the adaptive modelling scheme for this application has been described and a detailed mathematical evaluation has been employed to prove that such a scheme has the capability of extracting accurately the concentration of glucose from a complex biological media.
Li, Gang; Men, Jian-Long; Sun, Zhao-Min; Wang, Hui-Quan; Lin, Ling; Tong, Ying; Zhang, Bao-Ju
Time-varying noises in spectra collection process have influence on the prediction accuracy of quantitative calibration in the non-invasive blood components measurement which is based on dynamic spectrum (DS) method. By wavelet transform, we focused on the absorbance wave of fingertip transmission spectrum in pulse frequency band. Then we increased the signal to noise ratio of DS data, and improved the detecting precision of quantitative calibration. After carrying out spectrum data continuous acquisition of the same subject for 10 times, we used wavelet transform de-noising to increase the average correlation coefficient of DS data from 0.979 6 to 0.990 3. BP neural network was used to establish the calibration model of subjects' blood components concentration values against dynamic spectrum data of 110 volunteers. After wavelet transform de-noising, the correlation coefficient of prediction set increased from 0.677 4 to 0.846 8, and the average relative error was decreased from 15.8% to 5.3%. Experimental results showed that the introduction of wavelet transform can effectively remove the noise in DS data, improve the detecting precision, and accelerate the development of non-invasive blood components measurement based on DS method.
Ferradal, Silvina L.; Yuki, Koichi; Vyas, Rutvi; Ha, Christopher G.; Yi, Francesca; Stopp, Christian; Wypij, David; Cheng, Henry H.; Newburger, Jane W.; Kaza, Aditya K.; Franceschini, Maria A.; Kussman, Barry D.; Grant, P. Ellen
The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO2) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management. PMID:28276534
Kuribayashi, Ryosuke; Furukawa, Hiromitsu
By using a "slit-less" Fourier-transform spectrometer, we demonstrate that cardiac-pulsation amplitude of absorbance can be extracted from 3.5-level absorbance unit (AU) spectra of a human fingertip with a resolution of < 0.0005 AU and a spectral resolution of < several tens of nanometers, even with a low-cost "non-cooled" NIR detector. From the extracted spectrum over 1,000-1,400 nm, the average amounts of pulsating blood components (water, HbO2, and lipids/proteins) in a fingertip are deduced in the sub-milligram order. The results indicate the capacity of the spectrometer for a portable non-invasive blood monitor as well as for a high-end analytic instrument.
Mao, Jian-Min; Wright, Leigh P.; Elmandjra, Mohamed
Using a near-infrared optical device developed by ViOptix, Inc., a clinical study on post-operative non-invasive monitoring of finger blood perfusion has been conducted for 48 patients undergoing digital replantation at the California Pacific Medical Center. The study showed that non-survival digits have their tissue oxygen saturation (StO2) values significantly lower than those for the controls in general, but survival digits did not. Further, the StO2 values can be used to define a survival index, in terms of which a digit survival criterion was tentatively suggested. Applying the criterion to the 64 digits (with 3 of them non-survival) involved in the clinical study, the sensitivity and the specificity were high. Therefore the device may have potential to be used in post-operative monitoring for digit replantation.
Molhoek, G P; Wesseling, K H; Settels, J J; van Vollenhoven, E; Weeda, H W; de Wit, B; Arntzenius, A C
Blood pressure in the finger was measured by a servo-plethysmomanometer constructed after the design of Penàz, which uses the principle of the unloaded arterial wall. The device contains a photoelectric plethysmograph mounted in an inflatable cuff and an electro-pneumatic transducer to control air pressure in the cuff via a servosystem. Comparison of simultaneous measurements of intra-arterial pressure in the brachial artery was performed on 33 patients suspected of having hypertension. In 12 patients evaluation of the technique could not be carried out due to technical failures or distorted blood pressure wave forms. Results of the remaining 21 patients show a mean underestimation of intra-arterial blood pressure by finger cuff blood pressure of 0.8 kPa (6 mm Hg), both for systolic and diastolic levels. The scatter range of the difference is from 1.9 to -3.5 kPa for systolic and 0.1 to -2.5 kPa for diastolic values. It appears that, although not all technical problems are solved, the Penàz servo-plethysmo-manometer is potentially an elegant method by which to arrive at the fully calibrated wave form of blood pressure in a finger in a non-invasive and continuous fashion.
Krämer, Christina E. M.; Wiechert, Wolfgang; Kohlheyer, Dietrich
Conventional propidium iodide (PI) staining requires the execution of multiple steps prior to analysis, potentially affecting assay results as well as cell vitality. In this study, this multistep analysis method has been transformed into a single-step, non-toxic, real-time method via live-cell imaging during perfusion with 0.1 μM PI inside a microfluidic cultivation device. Dynamic PI staining was an effective live/dead analytical tool and demonstrated consistent results for single-cell death initiated by direct or indirect triggers. Application of this method for the first time revealed the apparent antibiotic tolerance of wild-type Corynebacterium glutamicum cells, as indicated by the conversion of violet fluorogenic calcein acetoxymethyl ester (CvAM). Additional implementation of this method provided insight into the induced cell lysis of Escherichia coli cells expressing a lytic toxin-antitoxin module, providing evidence for non-lytic cell death and cell resistance to toxin production. Finally, our dynamic PI staining method distinguished necrotic-like and apoptotic-like cell death phenotypes in Saccharomyces cerevisiae among predisposed descendants of nutrient-deprived ancestor cells using PO-PRO-1 or green fluorogenic calcein acetoxymethyl ester (CgAM) as counterstains. The combination of single-cell cultivation, fluorescent time-lapse imaging, and PI perfusion facilitates spatiotemporally resolved observations that deliver new insights into the dynamics of cellular behaviour. PMID:27580964
Gamella, M; Campuzano, S; Manso, J; González de Rivera, G; López-Colino, F; Reviejo, A J; Pingarrón, J M
A non-invasive, passive and simple to use skin surface based sensing device for determining the blood's ethanol content (BAC) by monitoring transdermal alcohol concentration (TAC) is designed and developed. The proposed prototype is based on bienzyme amperometric composite biosensors that are sensitive to the variation of ethanol concentration. The prototype correlates, through previous calibration set-up, the amperometric signal generated from ethanol in sweat with its content in blood in a short period of time. The characteristics of this sensor device permit determination of the ethanol concentration in isolated and in continuous form, giving information of the BAC of a subject either in a given moment or its evolution during long periods of time (8h). Moreover, as the measurements are performed in a biological fluid, the evaluated individual is not able to alter the result of the analysis. The maximum limit of ethanol in blood allowed by legislation is included within the linear range of the device (0.0005-0.6 g L(-1)). Moreover, the device shows higher sensitivity than the breathalyzers marketed at the moment, allowing the monitoring of the ethanol content in blood to be obtained just 5 min after ingestion of the alcoholic drink. The comparison of the obtained results using the proposed device in the analysis of 40 volunteers with those provided by the gas chromatographic reference method for determination of BAC pointed out that there were no significant differences between both methods.
Ates, Sezen Canim; Bagirova, Malahat; Allahverdiyev, Adil M; Kocazeybek, Bekir; Kosan, Erdogan
In recent years, the role of donor blood has taken an important place in epidemiology of Leishmaniasis. According to the WHO, the numbers of patients considered as symptomatic are only 5-20% of individuals with asymptomatic leishmaniasis. In this study for detection of Leishmania infection in donor blood samples, 343 samples from the Capa Red Crescent Blood Center were obtained and primarily analyzed by microscopic and serological methods. Subsequently, the traditional culture (NNN), Immuno-chromatographic test (ICT) and Polymerase Chain Reaction (PCR) methods were applied to 21 samples which of them were found positive with at least one method. Buffy coat (BC) samples from 343 blood donors were analyzed: 15 (4.3%) were positive by a microculture method (MCM); and 4 (1.1%) by smear. The sera of these 343 samples included 9 (2.6%) determined positive by ELISA and 7 (2%) positive by IFAT. Thus, 21 of (6.1%) the 343 subjects studied by smear, MCM, IFAT and ELISA techniques were identified as positive for leishmaniasis at least one of the techniques and the sensitivity assessed. According to our data, the sensitivity of the methods are identified as MCM (71%), smear (19%), IFAT (33%), ELISA (42%), NNN (4%), PCR (14%) and ICT (4%). Thus, with this study for the first time, the sensitivity of a MCM was examined in blood donors by comparing MCM with the methods used in the diagnosis of leishmaniasis. As a result, MCM was found the most sensitive method for detection of Leishmania parasites in samples obtained from a blood bank. In addition, the presence of Leishmania parasites was detected in donor bloods in Istanbul, a non-endemic region of Turkey, and these results is a vital importance for the health of blood recipients.
Stephen, Ian D; Coetzee, Vinet; Law Smith, Miriam; Perrett, David I
Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice.
Uwadaira, Yasuhiro; Ikehata, Akifumi; Momose, Akiko; Miura, Masayo
The “glucose-linked wavelength” in the short-wavelength near-infrared (NIR) region, in which the light intensity reflected from the hand palm exhibits a good correlation to the blood glucose value, was investigated. We performed 391 2-h carbohydrate tolerance tests (CTTs) using 34 participants and a glucose-linked wavelength was successfully observed in almost every CTT; however, this wavelength varied between CTTs even for the same person. The large resulting data set revealed the distribution of the informative wavelength. The blood glucose values were efficiently estimated by a simple linear regression with clinically acceptable accuracies. The result suggested the potential for constructing a personalized low-invasive blood glucose sensor using short-wavelength NIR spectroscopy. PMID:27446701
Sun, Meixiu; Chen, Nanguang
An optical spectroscopic method is investigated theoretically for in vivo measurement of blood glucose concentration. This method is based on dynamic dual wavelength (610 nm and 810 nm) time-resolved measurements under a condition of artificial blood flow kinetics in a human finger. The influence of glucose concentration on absorption and reduced scattering coefficients of the whole blood is simulated using the T-matrix method. The scattering centers, RBC aggregation, under the artificial — kinetics condition are modeled as spheroid. The modified parametric slopes were derived from the Laplace transformed data of the time-resolved transmittance. The results show that an appropriate selection of the Laplace parameter can lead to enhanced sensitivity for glucose measurement.
Serratia rubidea ns ns *** ns Proteus vulgaris ns ns ns ns Yersinia enterocolitica ns ns *** ns KEY: ns = not significant; * = p< 0.05; ** = p< 0.01...contamination in white cell-reduced and non-reduced platelets. Transfusion 33: 450-457 (1993) 11. Feng, P. et al. Direct identification of Yersinia ... enterocolitica in blood of polymerase chain reaction amplification. Tranqfusion 32: 850-854 (1992). 11 (9) Appendix: PAGEA TITLE IA Table 1- Selected
Jiang, Jingying; Zou, Da; Min, Xiaolin; Ma, Zhenhe; Xu, Kexin
With the changing of human diet and the future of an aging society, the number of diabetic patients is growing rapidly and steadily. The major therapeutic method to that disease is monitoring the blood glucose concentration frequently to adjust the dose of the drugs and insulin. In order to avoid the painful finger prick, we choose the ear lobe as a measurement site with finger as a reference. Firstly, we compare the blood glucose concentration results of ear lobe and finger during an oral glucose tolerance test, the results showed a good correlation of the two sites. Secondly, the three-layered skin structure of finger and ear lobe has been studied by using optical coherence tomography (OCT) technique. The result shows that the thickness of each layer at ear lobe is thinner. Finally, the difference between reflectance spectra of finger and ear lobe is compared due to the diverse skin thickness. The results still show a higher absorbance value for ear lobe. In conclusion, the ear lobe is an ideal measurement site for noninvasive blood glucose sensing.
Lambert, James L. (Inventor); Borchert, Mark S. (Inventor)
A non-invasive method for determining blood level of an analyte of interest, such as glucose, comprises: generating an excitation laser beam (e.g., at a wavelength of 700 to 900 nanometers); focusing the excitation laser beam into the anterior chamber of an eye of the subject so that aqueous humor in the anterior chamber is illuminated; detecting (preferably confocally detecting) a Raman spectrum from the illuminated aqueous humor; and then determining the blood glucose level (or the level of another analyte of interest) for the subject from the Raman spectrum. Preferably, the detecting step is followed by the step of subtracting a confounding fluorescence spectrum from the Raman spectrum to produce a difference spectrum; and determining the blood level of the analyte of interest for the subject from that difference spectrum, preferably using linear or nonlinear multivariate analysis such as partial least squares analysis. Apparatus for carrying out the foregoing method is also disclosed.
AlOmari, A H; Savkin, A V; Karantonis, D M; Lim, E; Lovell, N H
We propose dynamical models for pulsatile flow and head estimation in an implantable rotary blood pump. Pulsatile flow and head data were obtained using a circulatory mock loop where fluid solutions with different values of viscosities were used as a blood analogue with varying haematocrit (HCT). Noninvasive measurements of power and pump speed were used with HCT values as inputs to the flow model while the estimated flow was used with the speed as inputs to a head estimation model. Linear regression analysis between estimated and measured flows obtained from a mock loop resulted in a highly significant correlation (R2=0.982) and a mean absolute error (e) of 0.323 L min(-1), while for head, R2=0.933 and e=7.682 mmHg were obtained. R2=0.849 and e=0.584 L min(-1) were obtained when the same model derived in the mock loop was used for flow estimation in ex vivo porcine data (N=6). Furthermore, in the steady state, the solution of the presented flow model can be described by a previously designed and verified static model. The models developed herein will play a vital role in developing a robust control system of the pump flow coping with changing physiological demands.
Moradi, Shabnam Zarei; Masoudi, Najmehsadat; Mohseni Meybodi, Anahita; Anisi Hemaseh, Khadijeh; Mozafari Kermani, Ramin; Shahzadeh Fazeli, Abolhasan; Gourabi, Hamid
Background: To verify the hypothesis that the incidence of chromosomal abnormalities increases in babies conceived by different assisted reproduction procedures. The availability of the umbilical cord blood encouraged us to study this hypothesis via this method. Materials and Methods: This is a descriptive study, umbilical cord blood samples of assisted reproductive technology (ART) children were analyzed with standard cytogenetic techniques (G banding). Karyotyping was possible in 109 cases. Results: The number of abnormal cases was four (3.7%), among which, three cases (2.8%) were inherited and only 1 case (0.9%) was a de novo translocation. In total, the incidence of de novo chromosomal abnormalities was in the range observed in all live births in the general population (0.7-1%). Conclusion: No significant difference in the incidence of chromosomal abnormality was found between ART and naturally conceived babies. To date, several studies have examined the medical and developmental outcome of ART children and still have not reached a definite conclusion. Genetic counseling is recommended as an integral part of planning of treatment strategies for couples wishing to undergo ART. PMID:27695612
Stuebner, Eva; Vichayanrat, Ekawat; Low, David A.; Mathias, Christopher J.; Isenmann, Stefan; Haensch, Carl-Albrecht
Non-motor symptoms are now commonly recognized in Parkinson’s disease (PD) and can include dysautonomia. Impairment of cardiovascular autonomic function can occur at any stage of PD but is typically prevalent in advanced stages or related to (anti-Parkinsonian) drugs and can result in atypical blood pressure (BP) readings and related symptoms such as orthostatic hypotension (OH) and supine hypertension. OH is usually diagnosed with a head-up-tilt test (HUT) or an (active) standing test (also known as Schellong test) in the laboratory, but 24 h ambulatory blood pressure monitoring (ABPM) in a home setting may have several advantages, such as providing an overview of symptoms in daily life alongside pathophysiology as well as assessment of treatment interventions. This, however, is only possible if ABPM is administrated correctly and an autonomic protocol (including a diary) is followed which will be discussed in this review. A 24-h ABPM does not only allow the detection of OH, if it is present, but also the assessment of cardiovascular autonomic dysfunction during and after various daily stimuli, such as postprandial and alcohol dependent hypotension, as well as exercise and drug induced hypotension. Furthermore, information about the circadian rhythm of BP and heart rate (HR) can be obtained and establish whether or not a patient has a fall of BP at night (i.e., “dipper” vs. non-“dipper”). The information about nocturnal BP may also allow the investigation or detection of disorders such as sleep dysfunction, nocturnal movement disorders, and obstructive sleep apnea, which are common in PD. Additionally, a 24-h ABPM should be conducted to examine the effectiveness of OH therapy. This review will outline the methodology of 24 h ABPM in PD, summarize findings of such studies in PD, and briefly consider common daily stimuli that might affect 24 h ABPM. PMID:23720648
De Mey, C; Schroeter, V; Butzer, R; Roll, S; Belz, G G
1. The agreement of blood pressure measurements by stethoscope auscultation (SBPa, DBPa-IV and DBPa-V), oscillometry (Dinamap; SBPo, and DBPo) and digital photoplethysmography (Finapres; SBPf, and DBPf) with the graphical analysis of the analogue microphone signals of vascular wall motion sound (SBPg and DBPg) was evaluated in eight healthy subjects in the presence of responses to the intravenous infusion of 1 microgram min-1 isoprenaline. 2. In general, there was good agreement between the SBP/DBP-measurements based on auscultatory Korotkoff-I- and IV-criteria and the reference method; the average method difference in estimating the isoprenaline responses for SBPa-SBPg was: -1.1, 95% CI: -5.4 to 3.1 mm Hg with a within-subject between-method repeatability coefficient (REP) of 11.6 mm Hg and for DBPa-IV-DBPg: 3.5, 95% CI: -0.5 to 6.5 mm Hg, REP: 11.5 mm Hg. The ausculatation of Korotkoff-V substantially overestimated the isoprenaline induced reduction of DBP: method difference DBPa-V-DBPg: -11.3, 95% CI: -17.8 to -4.7 mm Hg, REP: 31.8 mm Hg. 3. Oscillometry yielded good approximations for the SBP response to isoprenaline (average method difference SBPo-SBPg: -2.9, 95% CI: -9.0 to 3.3 mm Hg, REP: 17.6 mm Hg) but was poorly sensitive with regard to the DBP responses: method difference DBPo-DBPg: 6.5, 95% CI: -1.3 to 14.3 mm Hg, REP: 25.7 mm Hg. 4. Whilst the finger pulse pressure agreed well with regard to DBP (method difference for the DBP responses to isoprenaline: DBPf-DBPg: 1.8, 95% CI: -5.1 to 8.6 mm Hg, REP: 18.5 mm Hg) it was rather unsatisfactory with regard to SBP (method difference SBPf-SBPg: -14.1, 95% CI: -28.2 to -0.1 mm Hg, REP: 49.9 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8554929
Uusitalo, A L; Tahvanainen, K U; Uusitalo, A J; Rusko, H K
We examined how the time and frequency domain measures of heart rate and blood pressure variability at supine rest reflect the sympathovagal balance of 23 female and male endurance athletes. Pharmacological blocking by atropine and propranolol was used as a standard for defining autonomic control of the heart. The Rosenblueth and Simeone model for neural control of heart rate was used to calculate the sympathovagal balance index (Abal). Atropinization significantly decreased all time and frequency domain measures of heart rate and blood pressure variability. beta-Blockade significantly decreased further the low- (< 0.07 Hz) and medium-frequency power (0.07-0.15 Hz) variability of R-R intervals (RRI) and SD of RRI. Abal was 0.629 +/- 0.019, indicating that parasympathetic activity predominated in the athletes. Basal heart rate (r = 0.519, P < 0.01), SD of RRI (r = -0.533, P < 0.01), root-mean-square of successive RRIs (RRI RMSSD) (r = -0.579, P < 0.05), RRI total (r = -0.557, P < 0.01) and RRI high-frequency (HF) power (r = -0.582, P < 0.01) correlated significantly with Abal and parasympathetic activity index. We concluded that the best non-invasive method of evaluating the sympathovagal balance of athletes at supine rest is to measure SD of RRI, RRI RMSSD, HF and total power of RRI variability. All heart rate variability measures were mainly parasympathetically modulated. The nature of blood pressure variability measures remained unclear and they could not be used to evaluate the sympathovagal balance among athletes.
Nance, Elizabeth; Timbie, Kelsie; Miller, G Wilson; Song, Ji; Louttit, Cameron; Klibanov, Alexander L; Shih, Ting-Yu; Swaminathan, Ganesh; Tamargo, Rafael J; Woodworth, Graeme F; Hanes, Justin; Price, Richard J
The blood-brain barrier (BBB) presents a significant obstacle for the treatment of many central nervous system (CNS) disorders, including invasive brain tumors, Alzheimer's, Parkinson's and stroke. Therapeutics must be capable of bypassing the BBB and also penetrate the brain parenchyma to achieve a desired effect within the brain. In this study, we test the unique combination of a non-invasive approach to BBB permeabilization with a therapeutically relevant polymeric nanoparticle platform capable of rapidly penetrating within the brain microenvironment. MR-guided focused ultrasound (FUS) with intravascular microbubbles (MBs) is able to locally and reversibly disrupt the BBB with submillimeter spatial accuracy. Densely poly(ethylene-co-glycol) (PEG) coated, brain-penetrating nanoparticles (BPNs) are long-circulating and diffuse 10-fold slower in normal rat brain tissue compared to diffusion in water. Following intravenous administration of model and biodegradable BPNs in normal healthy rats, we demonstrate safe, pressure-dependent delivery of 60nm BPNs to the brain parenchyma in regions where the BBB is disrupted by FUS and MBs. Delivery of BPNs with MR-guided FUS has the potential to improve efficacy of treatments for many CNS diseases, while reducing systemic side effects by providing sustained, well-dispersed drug delivery into select regions of the brain.
Avsenik, Jernej; Bisdas, Sotirios; Popovic, Katarina Surlan
Background. The blood-brain barrier represents the selective diffusion barrier at the level of the cerebral microvascular endothelium. Other functions of blood-brain barrier include transport, signaling and osmoregulation. Endothelial cells interact with surrounding astrocytes, pericytes and neurons. These interactions are crucial to the development, structural integrity and function of the cerebral microvascular endothelium. Dysfunctional blood-brain barrier has been associated with pathologies such as acute stroke, tumors, inflammatory and neurodegenerative diseases. Conclusions. Blood-brain barrier permeability can be evaluated in vivo by perfusion computed tomography - an efficient diagnostic method that involves the sequential acquisition of tomographic images during the intravenous administration of iodinated contrast material. The major clinical applications of perfusion computed tomography are in acute stroke and in brain tumor imaging. PMID:26029020
Crosignani, Andrea; Riva, Antonio; Della Bella, Silvia
Hepatitis C virus (HCV) has a high propensity to establish chronic infections. Failure of HCV-infected individuals to activate effective antiviral immune responses is at least in part related to HCV-induced impairment of dendritic cells (DCs) that play a central role in activating T cell responses. Although the impact of HCV on DC phenotype and function is likely to be more prominent in the liver, major HCV-induced alterations are detectable in peripheral blood DCs (pbDCs) that represent the most accessible source of DCs. These alterations include numerical reduction, impaired production of inflammatory cytokines and increased production of immunosuppressive IL10. These changes in DCs are relevant to our understanding the immune mechanisms underlying the propensity of HCV to establish persistent infection. Importantly, the non-invasive accessibility of pbDCs renders the analysis of these cells a convenient procedure that can be serially repeated in patient follow-up. Accordingly, the study of pbDCs in HCV-infected patients during conventional treatment with pegylated interferon and ribavirin indicated that restoration of normal plasmacytoid DC count may represent an additional mechanism contributing to the efficacy of the dual therapy. It also identified the pre-treatment levels of plasmacytoid DCs and IL10 as putative predictors of response to therapy. Treatment of chronic HCV infection is changing, as new generation direct-acting antiviral agents will soon be available for use in interferon-free therapeutic strategies. The phenotypic and functional analysis of pbDCs in this novel therapeutic setting will provide a valuable tool for investigating mechanisms underlying treatment efficacy and for identifying predictors of treatment response. PMID:26819508
Ragauskas, Arminas; Daubaris, Gediminas; Ragaisis, Vytautas; Petkus, Vytautas
The paper presents innovative methods and technology for non-invasive intracranial hemodynamics monitoring based on the measurement of brain parenchyma acoustic properties. The clinical investigation of new technology shows the similarity between the invasively recorded intracranial pressure (ICP) and non-invasively recorded intracranial blood volume (IBV) pulse waves, slow waves and slow trends under intensive care unit (ICU) conditions. Also, the applicability of the non-invasive IBV slow wave monitoring technique for cerebrovascular autoregulation non-invasive long-term monitoring is demonstrated by theoretical and experimental studies.
There are two little words, when taken together have great implications: ``What IF'' In the US alone, there are millions who are burdened with diabetes and who must maintain their glucose levels by taking blood samples and having it analyzed. Even though this procedure has improved over time, still it is very intrusive and is a burden to many that must live with it. What if it were not necessary? Although it is current practice to measure glucose levels invasively (using blood samples), it may be possible to measure glucose non-invasively. Although several companies around the world have invested millions of dollars to address this problem, none have been successful thus far. However, there are many methods that hold a potential and many approaches that have not yet been explored. We are working on a review of what has been approached thus far and are entertaining proposals for a combined interdisciplinary approach which combines expertise from bioengineering, physics, and biology. We hope to learn from the unsuccessful attempts of others whilst employing innovative new approaches to this problem.
Seymour, Roger S; Angove, Sophie E; Snelling, Edward P; Cassey, Phillip
The evolution of primates involved increasing body size, brain size and presumably cognitive ability. Cognition is related to neural activity, metabolic rate and rate of blood flow to the cerebral cortex. These parameters are difficult to quantify in living animals. This study shows that it is possible to determine the rate of cortical brain perfusion from the size of the internal carotid artery foramina in skulls of certain mammals, including haplorrhine primates and diprotodont marsupials. We quantify combined blood flow rate in both internal carotid arteries as a proxy of brain metabolism in 34 species of haplorrhine primates (0.116-145 kg body mass) and compare it to the same analysis for 19 species of diprotodont marsupials (0.014-46 kg). Brain volume is related to body mass by essentially the same exponent of 0.70 in both groups. Flow rate increases with haplorrhine brain volume to the 0.95 power, which is significantly higher than the exponent (0.75) expected for most organs according to 'Kleiber's Law'. By comparison, the exponent is 0.73 in marsupials. Thus, the brain perfusion rate increases with body size and brain size much faster in primates than in marsupials. The trajectory of cerebral perfusion in primates is set by the phylogenetically older groups (New and Old World monkeys, lesser apes) and the phylogenetically younger groups (great apes, including humans) fall near the line, with the highest perfusion. This may be associated with disproportionate increases in cortical surface area and mental capacity in the highly social, larger primates.
Bischoff, Farideh Z; Sinacori, Mina K; Dang, Dianne D; Marquez-Do, Deborah; Horne, Cassandra; Lewis, Dorothy E; Simpson, Joe Leigh
Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.
Joseph, Bellal; Haider, Ansab; Rhee, Peter
Technology has transformed the practice of medicine and surgery in particular over the last several decades. This change in practice has allowed diagnostic and therapeutic tests to be performed less invasively. Hemoglobin monitoring remains one of the most commonly performed diagnostic tests in the United States. Recently, non-invasive hemoglobin monitoring technology has gained popularity. The aim of this article is to review the principles of how this technology works, pros and cons, and the implications of non-invasive hemoglobin technology particularly in trauma surgery.
Retinal functional imager (RFI) is a unique non-invasive functional imaging system with novel capabilities for visualizing the retina. The objective of this review was to show the utility of non-invasive functional imaging in various disorders. Electronic literature search was carried out using the websites www.pubmed.gov and www.google.com. The search words were retinal functional imager and non-invasive retinal imaging used in combination. The articles published or translated into English were studied. The RFI directly measures hemodynamic parameters such as retinal blood-flow velocity, oximetric state, metabolic responses to photic activation and generates capillary perfusion maps (CPM) that provides retinal vasculature detail similar to flourescein angiography. All of these parameters stand in a direct relationship to the function and therefore the health of the retina, and are known to be degraded in the course of retinal diseases. Detecting changes in retinal function aid early diagnosis and treatment as functional changes often precede structural changes in many retinal disorders.
Fujita, S; Tamazawa, M; Kuroda, K
The effects of the blood perfusion rate on the optimization of heating conditions in radio-frequency capacitive hyperthermia were examined using numerical simulations. When the blood perfusion rate in the tumor was smaller than approximately one-half that of normal tissues, optimal selective heating of the tumor was obtained.
Hollwarth, M.E.; Smith, M.; Kvietys, P.R.; Granger, D.N.
The radioactive microsphere technique was used to estimate blood flow to different regions of the esophagus and to adjacent regions of the stomach before and after perfusion of the esophagus with hydrochloric acid (pH 1.5) for 5 min. Under resting conditions total blood flow, as well as blood flow to the mucosal-submucosal layer and the muscular layer, to both sphincters was significantly higher than to the esophageal body. Blood flow to the adjacent regions of the stomach was significantly higher than esophageal blood flow. Acid perfusion resulted in a large increase in total blood flow in both sphincters and the lower esophageal body. Gastric blood flow was not altered by acid perfusion. The esophageal hyperemia resulted primarily from an increase in blood flow to the muscular layer; mucosal-submucosal blood flow was increased only in the lower esophageal sphincter. The present study indicates that short periods (5 min) of gastroesophageal reflux may increase esophageal blood flow.
Hu, Zizhong; Zhang, Haonan; Mordovanakis, Aghapi; Paulus, Yannis M.; Liu, Qinghuai; Wang, Xueding; Yang, Xinmai
Antivascular therapy represents a proven strategy to treat angiogenesis. By applying synchronized ultrasound bursts and nanosecond laser irradiation, we developed a novel, selective, non-invasive, localized antivascular method, termed photo-mediated ultrasound therapy (PUT). PUT takes advantage of the high native optical contrast among biological tissues and can treat microvessels without causing collateral damage to the surrounding tissue. In a chicken yolk sac membrane model, under the same ultrasound parameters (1 MHz at 0.45 MPa and 10 Hz with 10% duty cycle), PUT with 4 mJ/cm2 and 6 mJ/cm2 laser fluence induced 51% (p = 0.001) and 37% (p = 0.018) vessel diameter reductions respectively. With 8 mJ/cm2 laser fluence, PUT would yield vessel disruption (90%, p < 0.01). Selectivity of PUT was demonstrated by utilizing laser wavelengths at 578 nm or 650 nm, where PUT selectively shrank veins or occluded arteries. In a rabbit ear model, PUT induced a 68.5% reduction in blood perfusion after 7 days (p < 0.001) without damaging the surrounding cells. In vitro experiments in human blood suggested that cavitation may play a role in PUT. In conclusion, PUT holds significant promise as a novel non-invasive antivascular method with the capability to precisely target blood vessels. PMID:28074839
Hu, Zizhong; Zhang, Haonan; Mordovanakis, Aghapi; Paulus, Yannis M.; Liu, Qinghuai; Wang, Xueding; Yang, Xinmai
Antivascular therapy represents a proven strategy to treat angiogenesis. By applying synchronized ultrasound bursts and nanosecond laser irradiation, we developed a novel, selective, non-invasive, localized antivascular method, termed photo-mediated ultrasound therapy (PUT). PUT takes advantage of the high native optical contrast among biological tissues and can treat microvessels without causing collateral damage to the surrounding tissue. In a chicken yolk sac membrane model, under the same ultrasound parameters (1 MHz at 0.45 MPa and 10 Hz with 10% duty cycle), PUT with 4 mJ/cm2 and 6 mJ/cm2 laser fluence induced 51% (p = 0.001) and 37% (p = 0.018) vessel diameter reductions respectively. With 8 mJ/cm2 laser fluence, PUT would yield vessel disruption (90%, p < 0.01). Selectivity of PUT was demonstrated by utilizing laser wavelengths at 578 nm or 650 nm, where PUT selectively shrank veins or occluded arteries. In a rabbit ear model, PUT induced a 68.5% reduction in blood perfusion after 7 days (p < 0.001) without damaging the surrounding cells. In vitro experiments in human blood suggested that cavitation may play a role in PUT. In conclusion, PUT holds significant promise as a novel non-invasive antivascular method with the capability to precisely target blood vessels.
Yalcin, Ozlem; Meiselman, Herbert J; Armstrong, Jonathan K; Baskurt, Oguz K
The role of red blood cell (RBC) aggregation as a determinant of in vivo blood flow is still unclear. This study was designed to investigate the influence of a well-controlled enhancement of RBC aggregation on blood flow resistance in an isolated-perfused heart preparation. Guinea pig hearts were perfused through a catheter inserted into the root of the aorta using a pressure servo-controlled pump system that maintained perfusion pressures of 30 to 100 mmHg. The hearts were beating at their intrinsic rates and pumping against the perfusion pressure. RBC aggregation was increased by Pluronic (F98) coating of RBC at a concentration 0.025 mg/ml, corresponding to about a 100% increment in RBC aggregation as measured by erythrocyte sedimentation rate. Isolated heart preparations were perfused with 0.40 l/l hematocrit unmodified guinea pig blood and with Pluronic-coated RBC suspensions in autologous plasma. At high perfusion pressures there were no significant differences between the flow resistance values for the two perfusates, with differences in flow resistance only becoming significant at lower perfusion pressures. These results can be interpreted to reflect the shear dependence of RBC aggregation: higher shear forces associated with higher perfusion pressures should have dispersed RBC aggregates resulting in blood flow resistances similar to control values. Experiments repeated in preparations in which the smooth muscle tone was inhibited by pre-treatment with papaverine indicated that significant effects of enhanced RBC aggregation could be detected at higher perfusion pressures, underlining the compensatory role of vasomotor control mechanisms.
Hu, Huiying; Jiang, Yulin; Zhang, Minghui; Liu, Shanying; Hao, Na; Zhou, Jing; Liu, Juntao; Zhang, Xiaojin; Ma, Liangkun
To evaluate, side by side, the efficiency of dried blood spots (DBSs) against serum screening for Down's syndrome, and then, to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down's syndrome. One thousand eight hundred and thirty-seven low-risk Chinese women, with singleton pregnancy, were enrolled for the study. Alpha-fetoprotein and free beta human chorionic gonadotropin were measured for the serum as well as for the parallel DBS samples. Partial high-risk pregnant women identified by primary blood testing (n = 38) were also subject to the secondary cfDNA screening. Diagnostic amniocentesis was utilized to confirm the screening results. The true positive rate for Down's syndrome detection was 100% for both blood screening methods; however, the false-positive rate was 3.0% for DBS and 4.0% for serum screening, respectively. DBS correlated well with serum screening on Down's syndrome detection. Three out of 38 primary high-risk women displayed chromosomal abnormalities by cfDNA analysis, which were confirmed by amniocentesis. Either the true detection rate or the false-positive rate for Down's syndrome between DBS and the serum test is comparable. In addition, blood primary screening aligned with secondary cfDNA analysis, a "before and after" two-tier screening strategy, can massively decrease the false-positive rate, which, then, dramatically reduces the demand for invasive diagnostic operation. Impact statement Children born with Down's syndrome display a wide range of mental and physical disability. Currently, there is no effective treatment to ease the burden and anxiety of the Down's syndrome family and the surrounding society. This study is to evaluate the efficiency of dried blood spots against serum screening for Down's syndrome and to construct a two-tier strategy by topping up the fetal
Kim, Junghoon; Whyte, John; Patel, Sunil; Avants, Brian; Europa, Eduardo; Wang, Jiongjiong; Slattery, John; Gee, James C; Coslett, H Branch; Detre, John A
Non-invasive measurement of resting state cerebral blood flow (CBF) may reflect alterations of brain structure and function after traumatic brain injury (TBI). However, previous imaging studies of resting state brain in chronic TBI have been limited by several factors, including measurement in relative rather than absolute units, use of crude spatial registration methods, exclusion of subjects with substantial focal lesions, and exposure to ionizing radiation, which limits repeated assessments. This study aimed to overcome those obstacles by measuring absolute CBF with an arterial spin labeling perfusion fMRI technique, and using an image preprocessing protocol that is optimized for brains with mixed diffuse and focal injuries characteristic of moderate and severe TBI. Resting state CBF was quantified in 27 individuals with moderate to severe TBI in the chronic stage, and 22 demographically matched healthy controls. In addition to global CBF reductions in the TBI subjects, more prominent regional hypoperfusion was found in the posterior cingulate cortices, the thalami, and multiple locations in the frontal cortices. Diffuse injury, as assessed by tensor-based morphometry, was mainly associated with reduced CBF in the posterior cingulate cortices and the thalami, where the greatest volume losses were detected. Hypoperfusion in superior and middle frontal cortices, in contrast, was associated with focal lesions. These results suggest that structural lesions, both focal and diffuse, are the main contributors to the absolute CBF alterations seen in chronic TBI, and that CBF may serve as a tool to assess functioning neuronal volume. We also speculate that resting reductions in posterior cingulate perfusion may reflect alterations in the default-mode network, and may contribute to the attentional deficits common in TBI.
Matsui, T; Hattori, H; Takase, B; Ishihara, M
In order to conduct non-contact estimation of arterial blood pH after massive haemorrhage, we calculated the arterial pH based on linear-regression analysis of exhaled gas concentrations (CO and CO2) and vital signs (heart rate, respiratory rate, and surface temperature) measured using non-contact methods in hypovolemic animals.
Mastik, F.; Cate, F. J. ten; Neumann, H. A. M.; van der Steen, A. F. W.
We describe a contactless optical technique selectively enhancing superficial blood vessels below variously pigmented intact human skin by combining images in different spectral bands. Two CMOS-cameras, with apochromatic lenses and dual-band LED-arrays, simultaneously streamed Left (L) and Right (R) image data to a dual-processor PC. Both cameras captured color images within the visible range (VIS, 400–780 nm) and grey-scale images within the near infrared range (NIR, 910–920 nm) by sequentially switching between LED-array emission bands. Image-size-settings of 1280 × 1024 for VIS & 640 × 512 for NIR produced 12 cycles/s (1 cycle = 1 VIS L&R-pair + 1 NIR L&R-pair). Decreasing image-size-settings (640 × 512 for VIS and 320 × 256 for NIR) increased camera-speed to 25 cycles/s. Contrasts from below the tissue surface were algorithmically distinguished from surface shadows, reflections, etc. Thus blood vessels were selectively enhanced and back-projected into the stereoscopic VIS-color-image using either a 3D-display or conventional shutter glasses. As a first usability reconnaissance we applied this custom-built mobile stereoscopic camera for several clinical settings: • blood withdrawal; • vein inspection in dark skin; • vein detection through iodide; • varicose vein and nevi pigmentosum inspection. Our technique improves blood vessel visualization compared to the naked eye, and supports depth perception. PMID:17048103
Wang, L.; Yun, X.; Stanacevic, M.; Gouma, P. I.
Diabetes is a most common disease worldwide. Acetone in exhaled breath is a known biomarker of Type- 1 diabetes. An exhaled breath analyzer has been developed with the potential to diagnose diabetes as a non-invasive alternative of the currently used blood-based diagnostics. This device utilizes a chemiresistor based on ferroelectric tungsten oxide nanoparticles and detects acetone selectively in breath-simulated media. Real-time monitoring of the acetone concentration is feasible, potentially making this detector a revolutionary, non- invasive, diabetes diagnostic tool.
Corr, Stuart J.; Shamsudeen, Sabeel; Vergara, Leoncio A.; Ho, Jason Chak-Shing; Ware, Matthew J.; Keshishian, Vazrik; Yokoi, Kenji; Savage, David J.; Meraz, Ismail M.; Kaluarachchi, Warna; Cisneros, Brandon T.; Raoof, Mustafa; Nguyen, Duy Trac; Zhang, Yingchun; Wilson, Lon J.; Summers, Huw; Rees, Paul; Curley, Steven A.; Serda, Rita E.
Herein, we present a novel imaging platform to study the biological effects of non-invasive radiofrequency (RF) electric field cancer hyperthermia. This system allows for real-time in vivo intravital microscopy (IVM) imaging of radiofrequency-induced biological alterations such as changes in vessel structure and drug perfusion. Our results indicate that the IVM system is able to handle exposure to high-power electric-fields without inducing significant hardware damage or imaging artifacts. Furthermore, short durations of low-power (< 200 W) radiofrequency exposure increased transport and perfusion of fluorescent tracers into the tumors at temperatures below 41°C. Vessel deformations and blood coagulation were seen for tumor temperatures around 44°C. These results highlight the use of our integrated IVM-RF imaging platform as a powerful new tool to visualize the dynamics and interplay between radiofrequency energy and biological tissues, organs, and tumors. PMID:26308617
Hu, Zhaoyan; Pan, Youlian; Chen, Zhenglong; Zhang, Tianyi; Lu, Lijun
This paper is aimed to study the optimal selection of structure of vaneless centrifugal blood pump. The optimal objective is determined according to requirements of clinical use. Possible schemes are generally worked out based on structural feature of vaneless centrifugal blood pump. The optimal structure is selected from possible schemes with constraints on blood perfusion and blood damage indexes. Using an optimal selection method one can find the optimum structure scheme from possible schemes effectively. The results of numerical simulation of optimal blood pump showed that the method of constraints of blood perfusion and blood damage is competent for the requirements of selection of the optimal blood pumps.
Zheng, Wei; Wang, Zhifeng; Shen, Li; Gao, Ling; Ford, James C.; Makedon, Fillia S.; Pearlman, Justin D.
With perfusion magnetic resonance imaging (pMRI), perfusion describes the amount of blood passing through a block of tissue in a certain period of time. In pMRI, the tissue having more blood passing through will show higher intensity value as more contrast-labeled blood arrives. Perfusion reflects the delivery of essential nutrients to a block of tissue, and is an important parameter for the tissue status. Considering solitary pulmonary nodules (SPN), perfusion differences between malignant and benign nodules have been studied by different techniques. Much effort has been put into its characterization. In this paper, we proposed and implemented extraction of the SPN time intensity profile to measure blood delivery to solitary pulmonary nodules, describing their perfusion effects. In this method, a SPN time intensity profile is created based on intensity values of the solitary pulmonary nodule in lung pMRI images over time. This method has two steps: nodule tracking and profile clustering. Nodule tracking aligns the solitary pulmonary nodule in pMRI images taken at different time points, dealing with nodule movement resulted from breathing and body movement. Profile clustering implements segmentation of the nodule region and extraction of the time intensity profile of a solitary pulmonary nodule. SPN time intensity profiles reflect patterns of blood delivery to solitary pulmonary nodules, giving us a description of perfusion effect and indirect evidence of tumor angiogenesis. Analysis on SPN time intensity profiles will help the diagnosis of malignant nodules for early lung cancer detection.
Aristovich, Ekaterina; Khan, Sanowar
This paper concerns detection of particle concentration (e.g. cholesterol) in conductive media (e.g. human blood) by impedance technique. The technique is based on changes in the impedance measurement across a given conducting medium due to changes in the particle concentration. The impedance is calculated by calculating the current through the conducting media produced by electric field distribution between two electrodes. This is done by modelling and computation of 3D electric fields between the electrodes for known voltages applied between them using the well-known finite element method (FEM). The complexity of such FE models is attributed to particle distribution, their geometric and material parameters, and their shape and size which can be of many orders of magnitude smaller than the overall problem domain under investigation. This paper overcomes this problem by adopting an effective particle coagulation (aggregation) strategy in FE modelling without significantly affecting the accuracy of field computation.
Litvinova, Karina S.; Ahmad, Shakil; Wang, Keqing; Rafailov, Ilya E.; Sokolovski, Sergei G.; Zhang, Lin; Rafailov, Edik U.; Ahmed, Asif
Endothelial dysfunction is directly linked to preeclampsia, a maternal hypertensive condition that is life threating for both the mother and the baby. Epidemiological studies show that women with a history of pre-eclampsia have an elevated risk for cardiovascular disease. Here we report a new non-invasive diagnostic test for preeclampsia in mice that allows us to non-invasively assess the condition of the animals during the experiment and treatment in established models of preeclampsia. A laser-based multifunctional diagnostics system (LAKK-M) was chosen to carry out non-invasive analysis of multiple parameters. The device was used to simultaneously record the microcirculatory blood flow and oxygen saturation, as well as fluorescence levels of endogenous fluorophores. Preliminary experiments were conducted on adenoviral (Ad-)- mediated overexpression of sFlt-1 (Ad-sFlt-1) to mimic preeclampsialike symptoms in mice. The recorded data displayed the ability of the LAKK-M diagnostics device to detect significant differences in perfusion measurements between the control and Ad-sFlt-1 treatment. Preliminary results provide a potential avenue to employ these diagnostics technology to monitor and aid in maintaining control of live animal conditions throughout the experiment and treatment.
Lin, Chung-Yin; Hsieh, Han-Yi; Chen, Chiung-Mei; Wu, Shang-Rung; Tsai, Chih-Hung; Huang, Chiung-Yin; Hua, Mu-Yi; Wei, Kuo-Chen; Yeh, Chih-Kuang; Liu, Hao-Li
Focused ultrasound (FUS)-induced with microbubbles (MBs) is a promising technique for noninvasive opening of the blood-brain barrier (BBB) to allow targeted delivery of therapeutic substances into the brain and thus the noninvasive delivery of gene vectors for CNS treatment. We have previously demonstrated that a separated gene-carrying liposome and MBs administration plus FUS exposure can deliver genes into the brain, with the successful expression of the reporter gene and glial cell line-derived neurotrophic factor (GDNF) gene. In this study, we further modify the delivery system by conjugating gene-carrying liposomes with MBs to improve the GDNF gene-delivery efficiency, and to verify the possibility of using this system to perform treatment in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal disease model. FUS-BBB opening was verified by contrast-enhanced MRI, and GFP gene expression was verified via in vivo imaging system (IVIS). Western blots as well as enzyme-linked immunosorbent assay (ELISA) were conducted to measure protein expression, and immunohistochemistry (IHC) was conducted to test the Tyrosine hydroxylase (TH)-neuron distribution. Dopamine (DA) and its metabolites as well as dopamine active transporter (DAT) were quantitatively analyzed to show dopaminergic neuronal dopamine secretion/activity/metabolism. Motor performance was evaluated by rotarod test weekly. Results demonstrated that the LpDNA-MBs (gene-liposome-MBs) complexes successfully serve as gene carrier and BBB-opening catalyst, and outperformed the separated LpDNA/MBs administration both in terms of gene delivery and expression. TH-positive IHC and measurement of DA and its metabolites DOPAC and HVA confirmed improved neuronal function, and the proposed system also provided the best neuroprotective effect to retard the progression of motor-related behavioral abnormalities. Immunoblotting and histological staining further confirmed the expression of reporter genes in
Yoshino, M.; Kamada, K.; Shoji, Y.; Yoshikawa, A.; Shimazoe, K.; Lipovec, A.; Takahashi, H.; Fujiwara, K.; Takahashi, M.; Momose, T.; Ito, S.; Tsutsumi, K.; Endo, T.; Sato, H.; Usuki, Y.
We developed Time-over-Threshold based digital PET (TODPET2) tomograph using silicon photomultipliers (SiPM) arrays coupled with pixelized Ce:Gd3(Ga, Al)5O12 (Ce:GAGG) scintillators dedicated for non-invasive measurement of blood RI concentrations. The detector consists of 1.57 × 1.57 mm2 SiPM chips and 1.6 × 1.6 × 15 mm3 Ce:GAGG scintillators arranged on a 12 × 12 channel, both working as individual readout systems. After the development of the detector, we fabricated the PET gantry composed of 8 pieces of SiPM/Ce:GAGG detector array which signals were sent to the current-comparing type time-over-threshold (TOT) ASIC for individual readout of pixels. The PET scanner which we developed has 25 mm axial field-of-view (FOV) and 60 mm transaxial FOV. The spatial resolution reconstructed with maximum likelihood estimation method (MLEM) is 0.98 mm (FWHM) at the center of FOV. The sensitivity of the system is measured to be 1.31% using 22Na point source. Finally, timing response to changes in RI concentration was also measured using 5 mm diameter syringe injected with several concentrations of 18FDG.
Kitamura, Shingo; Shirota, Minori; Fukuda, Wakako; Inamura, Takao; Fukuda, Ikuo
Computational numerical analysis was performed to elucidate the flow dynamics of femoral artery perfusion. Numerical simulation of blood flow was performed from the right femoral artery in an aortic model. An incompressible Navier-Stokes equation and continuity equation were solved using computed flow dynamics software. Three different perfusion models were analyzed: a 4.0-mm cannula (outer diameter 15 French size), a 5.2-mm cannula (18 French size) and an 8-mm prosthetic graft. The cannula was inserted parallel to the femoral artery, while the graft was anastomosed perpendicular to the femoral artery. Shear stress was highest with the 4-mm cannula (172 Pa) followed by the graft (127 Pa) and the 5.2-mm cannula (99 Pa). The cannula exit velocity was high, even when the 5.2-mm cannula was used. Although side-armed perfusion with an 8-mm graft generated a high shear stress area near the point of anastomosis, flow velocity at the external iliac artery was decreased. The jet speed decreased due to the Coanda effect caused by the recirculation behind sudden expansion of diameter, and the flow velocity maintains a constant speed after the reattachment length of the flow. This study showed that iliac artery shear stress was lower with the 5.2-mm cannula than with the 4-mm cannula when used for femoral perfusion. Side-armed graft perfusion generates a high shear stress area around the anastomotic site, but flow velocity in the iliac artery is slower in the graft model than in the 5.2-mm cannula model.
Wälchli, Thomas; Mateos, José María; Weinman, Oliver; Babic, Daniela; Regli, Luca; Hoerstrup, Simon P; Gerhardt, Holger; Schwab, Martin E; Vogel, Johannes
During development and in various diseases of the CNS, new blood vessel formation starts with endothelial tip cell selection and vascular sprout migration, followed by the establishment of functional, perfused blood vessels. Here we describe a method that allows the assessment of these distinct angiogenic steps together with antibody-based protein detection in the postnatal mouse brain. Intravascular and perivascular markers such as Evans blue (EB), isolectin B4 (IB4) or laminin (LN) are used alongside simultaneous immunofluorescence on the same sections. By using confocal laser-scanning microscopy and stereological methods for analysis, detailed quantification of the 3D postnatal brain vasculature for perfused and nonperfused vessels (e.g., vascular volume fraction, vessel length and number, number of branch points and perfusion status of the newly formed vessels) and characterization of sprouting activity (e.g., endothelial tip cell density, filopodia number) can be obtained. The entire protocol, from mouse perfusion to vessel analysis, takes ∼10 d.
Wang, Ruikang K.
Optical micro-angiography (OMAG) is a recently developed method of imaging localized blood perfusion at capillary level resolution within microcirculatory beds. This paper reports that the OMAG is capable of directional blood perfusion mapping in vivo. This is achieved simply by translating the mirror located in the reference arm back and forth while 3D imaging is performed. The mirror which moves toward the incident beam gives the blood perfusion that flows away from the beam direction and vice versa. The approach is experimentally demonstrated by imaging of a flow phantom and then cerebro-vascular perfusion of a live mouse with cranium intact.
Thews, O; Hummel, M; Kelleher, D K; Lecher, B; Vaupel, P
Isolated limb perfusion allows the direct application of therapeutic agents to a tumour-bearing extremity. The present study investigated whether the dihydropyridine-type Ca(2+)-channel blocker nifedipine could improve blood flow and oxygenation status of experimental tumours during isolated limb perfusion. Perfusion was performed by cannulation of the femoral artery and vein in rats bearing DS-sarcoma on the hind foot dorsum. Perfusion rate was adjusted to maintain a perfusion pressure of 100-140 mmHg throughout the experiment. Following equilibration, nifedipine was continuously infused for 30 min (8.3 microg min(-1) kg(-1) BW). During constant-pressure isolated limb perfusion, nifedipine can significantly increase perfusion rate (+100%) and RBC flux (+60%) through experimental leg tumours. "Steal phenomena" in favour of the surrounding normal tissue and oedema formation were not observed. Despite the increased oxygen availability (+63%) seen upon application of this calcium channel blocker, nifedipine does not result in a substantial reduction of tumour hypoxia, most probably due to an increase in O(2) uptake with rising O(2) supply to the tumour-bearing hind limb. Nifedipine application during isolated limb perfusion can enhance tumour microcirculation and may therefore promote the delivery (pharmacokinetics) of anti-cancer drugs to the tumour and by this improve the efficacy of pressure-controlled isolated limb perfusion.
Xu, Qin-Yan; Yang, Jin-Sheng; Zhu, Bing; Yang, Li; Wang, Ying-Ying; Gao, Xin-Yan
Objective. We aim to study the therapeutic effects of scraping by investigating the changes of temperature and local blood perfusion volume in healthy subjects after scraping stimulation, and to explore the mechanism of scraping stimulation from the points of microcirculation and energy metabolism. Methods. Twenty-three health subjects were included in this study. Local blood perfusion volume and body surface temperature was detected at 5 min before scraping stimulation, 0, 15, 30, 60 and 90 min after scraping using Laser Doppler imager and infrared thermograph. Results. Significant increase was noted in the blood perfusion volume in the scraping area within 90 minutes compared to the baseline level and non-scraping area (P < 0.001). Compared with non-scraping area, an increase of body temperature with an average of 1°C was observed after scraping stimulation (P < 0.01). Conclusion. Scraping can significantly improve the blood perfusion volume and increase the temperature in the scraping area, promoting the local blood circulation and energy metabolism.
Cherecheanu, A Popa; Garhofer, G; Schmidl, D; Werkmeister, R; Schmetterer, L
Glaucoma is a progressive optic neuropathy of unknown origin. It has been hypothesized that a vascular component is involved in glaucoma pathophysiology. This hypothesis has gained support from studies showing that reduced ocular perfusion pressure is a risk factor for the disease. The exact nature of the involvement is, however, still a matter of debate. Based on recent evidence we propose a model including primary and secondary insults in glaucoma. The primary insult appears to happen at the optic nerve head. Increased intraocular pressure and ischemia at the post-laminar optic nerve head affects retinal ganglion cell axons. Modulating factors are the biomechanical properties of the tissues and cerebrospinal fluid pressure. After this primary insult retinal ganglion cells function at a reduced energy level and are sensitive to secondary insults. These secondary insults may happen if ocular perfusion pressure falls below the lower limit of autoregulation or if neurovascular coupling fails. Evidence for both faulty autoregulation and reduced hyperemic response to neuronal stimulation has been provided in glaucoma patients. The mechanisms appear to involve vascular endothelial dysfunction and impaired astrocyte-vessel signaling. A more detailed understanding of these pathways is required to direct neuroprotective strategies via the neurovascular pathway. PMID:23009741
Helton, Kathleen J.; Paydar, Amir; Glass, John; Weirich, Eric M.; Hankins, Jane; Li, Chin-Shang; Smeltzer, Matthew P.; Wang, Winfred C.; Ware, Russell E.; Ogg, Robert J.
Background Changes in cerebral perfusion are an important feature of the pathophysiology of sickle cell anemia (SCA); cerebrovascular ischemia occurs frequently and leads to neurocognitive deficits, silent infarcts, and overt stroke. Non-invasive MRI methods to measure cerebral blood flow (CBF) by arterial spin labeling (ASL) afford new opportunities to characterize disease- and therapy-induced changes in cerebral hemodynamics in patients with SCA. Recent studies have documented elevated gray matter (GM) CBF in untreated children with SCA, but no measurements of white matter (WM) CBF have been reported. Procedures Pulsed ASL with automated brain image segmentation-classification techniques were used to determine the CBF in GM, WM, and abnormal white matter (ABWM) of 21 children with SCA, 18 of whom were receiving hydroxyurea therapy. Results GM and WM CBF were highly associated (R2 =.76, p< 0.0001) and the GM to WM CBF ratio was 1.6 (95% confidence interval: 1.43-1.83). Global GM CBF in our treated cohort was 87 ± 24 mL/min/100 g, a value lower than previously reported in untreated patients with SCA. CBF was elevated in normal appearing WM (43 ± 14 mL/min/100 g) but decreased in ABWM (6 ± 12 mL/min/100 g), compared to published normal pediatric controls. Hemispheric asymmetry in CBF was noted in most patients. Conclusions These perfusion measurements suggest that hydroxyurea may normalize GM CBF in children with SCA, but altered perfusion in WM may persist. This novel combined approach for CBF quantification will facilitate prospective studies of cerebral vasculopathy in SCA, particularly regarding the effects of treatments such as hydroxyurea. PMID:18937311
Wang, Yang; West, John D.; Bailey, Jessica N.; Westfall, Daniel R.; Xiao, Hui; Arnold, Todd W.; Kersey, Patrick A.; Saykin, Andrew J.; McDonald, Brenna C.
We evaluated cerebral blood flow (CBF) in chronic pediatric mild traumatic brain injury (mTBI) using arterial spin labeling (ASL) magnetic resonance imaging perfusion. mTBI patients showed lower CBF than controls in bilateral frontotemporal regions, with no between-group cognitive differences. Findings suggest ASL may be useful to assess functional abnormalities in pediatric mTBI. PMID:25649779
Kandulla, Jochen; Elsner, Hanno; Sandeau, Julien; Birngruber, Reginald; Brinkmann, Ralf
In almost all retinal laser treatments the therapeutic effect is initiated by a transient temperature increase. Due to differences in tissue properties and physiology like pigmentation and vascular blood flow an individually different temperature increase might occur with crucial effects on the therapeutic benefit of the treatment. In order to determine the individual retinal temperature increase during cw-laser irradiation in real-time we developed a non-invasive method based on optoacoustics. Simultaneously to the cw-laser irradiation (λ = 810 nm, P < 3 W, t = 60 s) pulses from a dye laser (λ = 500 nm, τ = 3.5 ns, Ε ~ 5 μJ) are applied concentrically to the cw-laser spot on the eyeground. The absorption of the pulses lead to a consequent heating and thermoelastic expansion of the tissue. This causes the emission of an ultrasonic pressure wave, which amplitude was found to be temperature dependent following in good approximation a 2 nd order polynomial. The pressure wave was measured by an ultrasonic transducer embedded in a contact lens placed on the cornea. The experiments were performed in-vivo on rabbits. Simultaneous measurements with a miniaturized thermocouple showed a similar slope with a maximum local deviation of 0.4 °C for a temperature increase of 5.5 °C. On two rabbits measurements pre and post mortem at the same location were performed. The temperature increase after 60 s was found to raise by 12.0 % and 66.7 % post mortem, respectively. These data were used to calculate the influence of heat convection by blood circulation using a numerical model based on two absorbing layers and assuming a constant perfusion rate for the choriocapillaris and the choroid. Overall the presented optoacoustic method seems feasible for a non-invasive real-time determination of cw-laser induced retinal temperature increases and might serve as a temperature based dosimetry control during retinal laser treatments.
Calbet, José A. L.; Boushel, Robert; Helge, Jørn W.; Søndergaard, Hans; Munch‐Andersen, Thor; van Hall, Gerrit; Mortensen, Stefan P.; Secher, Niels H.
New Findings What is the central question of this study? Temperature‐sensitive mechanisms are thought to contribute to blood‐flow regulation, but the relationship between exercising and non‐exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism in exercising and non‐exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature‐ and metabolism‐sensitive mechanisms are important for the control of human limb perfusion, possibly by activating ATP release from the erythrocytes. Temperature‐sensitive mechanisms may contribute to blood‐flow regulation, but the influence of temperature on perfusion to exercising and non‐exercising human limbs is not established. Blood temperature (T B), blood flow and oxygen uptake (V˙O2) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise. During prolonged exercise, leg blood flow (LBF) was fourfold higher than arm blood flow (ABF) in association with higher T B and limb V˙O2. Leg and arm vascular conductance during exercise compared with rest was related closely to T B (r 2 = 0.91; P < 0.05), plasma ATP (r 2 = 0.94; P < 0.05) and limb V˙O2 (r 2 = 0.99; P < 0.05). During incremental leg exercise, LBF increased in association with elevations in T B and limb V˙O2, whereas ABF, arm T B and V˙O2 remained largely unchanged. During incremental arm exercise, both ABF and LBF increased in relationship to similar increases in V˙O2. In 12 trained males, increases in femoral T B and LBF during incremental leg exercise were mirrored by similar pulmonary artery T B and cardiac output dynamics, suggesting that processes in active limbs dominate central
Karanjia, Rustam N; Crossey, Mary M E; Cox, I Jane; Fye, Haddy K S; Njie, Ramou; Goldin, Robert D; Taylor-Robinson, Simon D
Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and non-invasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy. PMID:28018096
Brooks, W W; Apstein, C S
The effects of treppe on left ventricular function in the isolated mouse heart perfused with physiological buffer or with erythrocyte-rich buffer were compared. Left ventricular systolic and diastolic pressures were measured in the isovolumically contracting (balloon in the left ventricle) mouse hearts. Hearts were isolated from 12 adult Swiss-Webster mice and perfused at constant pressure (approximately 85 mmHg) via the aorta. Perfusate consisted of non-recirculating oxygenated Krebs-Henseleit (KH) solution without or with washed cow red blood cells at a hematocrit of 20% (KH-RBC20). The measured ionized calcium concentration of the perfusates were adjusted to 2.2 mmol/l and the temperature held constant at 37 degrees C. Left ventricular systolic pressure, its derivative and diastolic pressures were recorded via a pressure transducer attached to a small latex balloon which was placed in the left ventricle through a left atrial incision. The balloon volume was adjusted to achieve an end-diastolic pressure of 4-8 mmHg. Left ventricular (LV) developed pressure averaged 111 +/- 4 (mean +/- S.E.M.) with KH alone and 108 +/- 4 mmHg with KH-RBC20 while the coronary flows were 3.1 +/- 0.18 and 0.95 +/- 0.15 ml/min respectively. In both KH solution alone and KH-RBC20, developed pressure remained relatively stable from 3 to 5 Hz while +/- dp/dt increased approximately 10% above values observed at 3 Hz. During KH perfusion with increasing stimulation rates, left ventricular pressure and +/- dP/dt, to a lesser extent, decreased while end-diastolic pressure markedly increased at stimulation rates higher than 5 Hz. However, KH-RBC20 perfusion prevented the marked increase in diastolic pressure with increasing stimulation rates (from 5 to 10 Hz). No significant difference in left ventricular developed pressure or +/dP/dt response to treppe were in evidence between groups. These results demonstrate that diastolic function of the isovolumically contracting mouse heart is sensitive
Xiaobo, Zou; Xiaowei, Huang; Povey, Malcolm
Consumers and governments are increasingly interested in the safety, authenticity and quality of food commodities. This has driven attention towards non-invasive sensing techniques used for rapid analyzing these commodities. This paper provides an overview of the state of the art in, and available alternatives for, food assurance based on non-invasive sensing techniques. The main food quality traits of interest using non-invasive sensing techniques are sensory characteristics, chemical composition, physicochemical properties, health-protecting properties, nutritional characteristics and safety. A wide range of non-invasive sensing techniques, from optical, acoustical, electrical, to nuclear magnetic, X-ray, biosensor, microwave and terahertz, are organized according to physical principle. Some of these techniques are now in a period of transition between experimental and applied utilization and several sensors and instruments are reviewed. With continued innovation and attention to key challenges, such non-invasive sensors and biosensors are expected to open up new exciting avenues in the field of portable and wearable wireless sensing devices and connecting with mobile networks, thus finding considerable use in a wide range of food assurance applications. The need for an appropriate regulatory framework is emphasized which acts to exclude unwanted components in foods and includes needed components, with sensors as part of a reassurance framework supporting regulation and food chain management. The integration of these sensor modalities into a single technological and commercial platform offers an opportunity for a paradigm shift in food reassurance.
Baran, Utku; Li, Yuandong; Wang, Ruikang K.
Arteriolo-arteriolar anastomosis's role in regulating blood perfusion through penetrating arterioles during stroke is yet to be discovered. We apply ultra-high sensitive optical microangiography (UHS-OMAG) and Doppler optical microangiography (DOMAG) techniques to evaluate vessel diameter and red blood cell velocity changes in large number of pial and penetrating arterioles in relation with arteriolo-arteriolar anastomosis (AAA) during and after focal stroke. Thanks to the high sensitivity of UHS-OMAG, we were able to image pial microvasculature up to capillary level through a cranial window (9 mm2), and DOMAG provided clear image of penetrating arterioles up to 500μm depth. Results showed that penetrating arterioles close to a strong AAA connection dilate whereas penetrating arterioles constrict significantly in weaker AAA regions. These results suggest that AAA plays a major role in active regulation of the pial arterioles, and weaker AAA connections lead to poor blood perfusion to penumbra through penetrating arterioles.
Reinhart, Walter H; Piety, Nathaniel Z; Shevkoplyas, Sergey S
Red blood cells (RBCs) suspended in plasma form multicellular aggregates under low flow conditions, increasing apparent blood viscosity at low shear rates. It has previously been unclear, however, if RBC aggregation affects microvascular perfusion. Here we analyzed the impact of RBC aggregation on perfusion and 'capillary' hematocrit in an artificial microvascular network (AMVN) at driving pressures ranging from 5 to 60 cmH2 O to determine if aggregation could improve tissue oxygenation. RBCs were suspended at 30% hematocrit in either 46.5 g/L dextran 40 (D40, non-aggregating medium) or 35 g/L dextran 70 (D70, aggregating medium) solutions with equal viscosity. Aggregation was readily observed in the AMVN for RBCs suspended in D70 at driving pressures ≤ 40 cmH2 O. The AMVN perfusion rate was the same for RBCs suspended in aggregating and non-aggregating medium, at both 'venular' and 'capillary' level. Estimated 'capillary' hematocrit was higher for D70 suspensions than for D40 suspensions at intermediate driving pressures (5 - 40 cm H2 O). We conclude that although RBC aggregation did not affect the AMVN perfusion rate independently of the driving pressure, a higher hematocrit in the 'capillaries' of the network for D70 suspensions suggested a better oxygen transport capacity in the presence of RBC aggregation. This article is protected by copyright. All rights reserved.
Dremin, Victor V.; Sidorov, Victor V.; Krupatkin, Alexander I.; Galstyan, Gagik R.; Novikova, Irina N.; Zherebtsova, Angelina I.; Zherebtsov, Evgeny A.; Dunaev, Andrey V.; Abdulvapova, Zera N.; Litvinova, Karina S.; Rafailov, Ilya E.; Sokolovski, Sergei G.; Rafailov, Edik U.
Skin blood microcirculation and the metabolism activity of tissue were examined on the patients with type 2 diabetes. Laser Doppler flowmetry (LDF) with 1064 nm laser light source and fluorescence spectroscopy (FS) with excitation light of 365 nm and 450 nm have been used to monitor the blood perfusion and the content of coenzymes NADH and FAD. Concluding, the proposed combined LDF and tissue FS approach allows to identify the significant violations in the blood microcirculation and metabolic activity for type 2 diabetes patients.
Pilatou, Magdalena C.; Kolkman, Roy G. M.; Hondebrink, Erwin; Bolt, Rene A.; de Mul, Frits F. M.
To localize and monitor the blood content in tissue we developed a very sensitive photo-acoustical detector. PVDF has been used as piezo-electric material. In this detector also fibers for the illumination of the sample are integrated. Resolution is about 20 (m in depth and about 50-100 m laterally). We use 532 nm light. We will show how photoacoustics can be used for measuring the thickness of tissue above bone. We will also report measurements on tissue phantoms: e.g. a vessel delta from the epigastric artery branching of a Wistar rat, filled with an artificial blood-resembling absorber. The measurements have been carried out on phantoms containing vessels at several depths. Signal processing was enhanced by Fourier processing of the data.
Baba, Justin S; Akl, Tony; Cote, Gerard L.; Wilson, Mark A.; Ericson, Milton Nance
An implanted system is being developed to monitor transplanted liver health during the critical 7-10 day period posttransplantation. The unit will monitor organ perfusion and oxygen consumption using optically-based probes placed on both the inflow and outflow blood vessels, and on the liver parenchymal surface. Sensing probes are based on a 3- wavelength LED source and a photodiode detector. Sample diffuse reflectance is measured at 735, 805, and 940 nm. To ascertain optimal source-to-photodetector spacing for perfusion measurement in blood vessels, an ex vivo study was conducted. In this work, a dye mixture simulating 80% blood oxygen saturation was developed and perfused through excised porcine arteries while collecting data for various preset probe source-to-photodetector spacings. The results from this study demonstrate a decrease in the optical signal with decreasing LED drive current and a reduction in perfusion index signal with increasing probe spacing. They also reveal a 2- to 4-mm optimal range for blood vessel perfusion probe source-to-photodetector spacing that allows for sufficient perfusion signal modulation depth with maximized signal to noise ratio (SNR). These findings are currently being applied to guide electronic configuration and probe placement for in vivo liver perfusion porcine model studies.
Jäger, H. R.; Grieve, J. P.
Intra-arterial catheter angiography has, in the past, been the mainstay for the investigation of intracranial vascular disease. It is, however, invasive, usually requires in-patients admission, and is associated with a rate of neurological complications between 1% and 3%. In recent years, magnetic resonance angiography (MRA) and CT angiography (CTA) have emerged as non-invasive alternatives for imaging blood vessels and have made a significant impact on neuroradiological investigations. It is the purpose of this article to explain the basic technical principles of these two methods and to give an overview of their current clinical applications. PMID:10700757
Lacalle-Aurioles, María; Mateos-Pérez, José M; Guzmán-De-Villoria, Juan A; Olazarán, Javier; Cruz-Orduña, Isabel; Alemán-Gómez, Yasser; Martino, María-Elena; Desco, Manuel
The purpose of this study was to elucidate whether cerebral blood flow (CBF) can better characterize perfusion abnormalities in predementia stages of Alzheimer's disease (AD) than cerebral blood volume (CBV) and whether cortical atrophy is more associated with decreased CBV or with decreased CBF. We compared measurements of CBV, CBF, and mean cortical thickness obtained from magnetic resonance images in a group of healthy controls, patients with mild cognitive impairment (MCI) who converted to AD after 2 years of clinical follow-up (MCI-c), and patients with mild AD. A significant decrease in perfusion was detected in the parietal lobes of the MCI-c patients with CBF parametric maps but not with CBV maps. In the MCI-c group, a negative correlation between CBF values and cortical thickness in the right parahippocampal gyrus suggests an increase in CBF that depends on cortical atrophy in predementia stages of AD. Our study also suggests that CBF deficits appear before CBV deficits in the progression of AD, as CBV abnormalities were only detected at the AD stage, whereas CBF changes were already detected in the MCI stage. These results confirm the hypothesis that CBF is a more sensitive parameter than CBV for perfusion abnormalities in MCI-c patients.
Lacalle-Aurioles, María; Mateos-Pérez, José M; Guzmán-De-Villoria, Juan A; Olazarán, Javier; Cruz-Orduña, Isabel; Alemán-Gómez, Yasser; Martino, María-Elena; Desco, Manuel
The purpose of this study was to elucidate whether cerebral blood flow (CBF) can better characterize perfusion abnormalities in predementia stages of Alzheimer's disease (AD) than cerebral blood volume (CBV) and whether cortical atrophy is more associated with decreased CBV or with decreased CBF. We compared measurements of CBV, CBF, and mean cortical thickness obtained from magnetic resonance images in a group of healthy controls, patients with mild cognitive impairment (MCI) who converted to AD after 2 years of clinical follow-up (MCI-c), and patients with mild AD. A significant decrease in perfusion was detected in the parietal lobes of the MCI-c patients with CBF parametric maps but not with CBV maps. In the MCI-c group, a negative correlation between CBF values and cortical thickness in the right parahippocampal gyrus suggests an increase in CBF that depends on cortical atrophy in predementia stages of AD. Our study also suggests that CBF deficits appear before CBV deficits in the progression of AD, as CBV abnormalities were only detected at the AD stage, whereas CBF changes were already detected in the MCI stage. These results confirm the hypothesis that CBF is a more sensitive parameter than CBV for perfusion abnormalities in MCI-c patients. PMID:24424381
Ogami, M.; Kulkarni, R.; Wang, H.; Reif, R.; Wang, R. K.
We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as red blood cells from such stationary objects as surrounding tissue, to localise skin injury. This imaging technique provides detailed information about the acute perfusion response after a blood vessel is occluded. In this study, a mouse ear model is used and pulsed laser coagulation serves as the method of occlusion. We have found that the downstream blood vessels lacked blood flow due to occlusion at the target site immediately after injury. Relative flow changes in nearby collaterals and anastomotic vessels have been approximated based on differences in intensity in the nearby collaterals and anastomoses. We have also estimated the density of the affected downstream vessels. Laser speckle contrast imaging is shown to be used for highresolution and fast-speed imaging for the skin microvasculature. It also allows direct visualisation of the blood perfusion response to injury, which may provide novel insights to the field of cutaneous wound healing.
Ogami, M; Kulkarni, R; Wang, H; Reif, R; Wang, R K
We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as red blood cells from such stationary objects as surrounding tissue, to localise skin injury. This imaging technique provides detailed information about the acute perfusion response after a blood vessel is occluded. In this study, a mouse ear model is used and pulsed laser coagulation serves as the method of occlusion. We have found that the downstream blood vessels lacked blood flow due to occlusion at the target site immediately after injury. Relative flow changes in nearby collaterals and anastomotic vessels have been approximated based on differences in intensity in the nearby collaterals and anastomoses. We have also estimated the density of the affected downstream vessels. Laser speckle contrast imaging is shown to be used for highresolution and fast-speed imaging for the skin microvasculature. It also allows direct visualisation of the blood perfusion response to injury, which may provide novel insights to the field of cutaneous wound healing. (laser biophotonics)
Khoshnevis, Sepideh; Craik, Natalie K; Matthew Brothers, R; Diller, Kenneth R
The goal of this study was to investigate the persistence of cold-induced vasoconstriction following cessation of active skin-surface cooling. This study demonstrates a hysteresis effect that develops between skin temperature and blood perfusion during the cooling and subsequent rewarming period. An Arctic Ice cryotherapy unit (CTU) was applied to the knee region of six healthy subjects for 60 min of active cooling followed by 120 min of passive rewarming. Multiple laser Doppler flowmetry perfusion probes were used to measure skin blood flow (expressed as cutaneous vascular conductance (CVC)). Skin surface cooling produced a significant reduction in CVC (P < 0.001) that persisted throughout the duration of the rewarming period. In addition, there was a hysteresis effect between CVC and skin temperature during the cooling and subsequent rewarming cycle (P < 0.01). Mixed model regression (MMR) showed a significant difference in the slopes of the CVC-skin temperature curves during cooling and rewarming (P < 0.001). Piecewise regression was used to investigate the temperature thresholds for acceleration of CVC during the cooling and rewarming periods. The two thresholds were shown to be significantly different (P = 0.003). The results show that localized cooling causes significant vasoconstriction that continues beyond the active cooling period despite skin temperatures returning toward baseline values. The significant and persistent reduction in skin perfusion may contribute to nonfreezing cold injury (NFCI) associated with cryotherapy.
Khoshnevis, Sepideh; Craik, Natalie K.; Matthew Brothers, R.; Diller, Kenneth R.
The goal of this study was to investigate the persistence of cold-induced vasoconstriction following cessation of active skin-surface cooling. This study demonstrates a hysteresis effect that develops between skin temperature and blood perfusion during the cooling and subsequent rewarming period. An Arctic Ice cryotherapy unit (CTU) was applied to the knee region of six healthy subjects for 60 min of active cooling followed by 120 min of passive rewarming. Multiple laser Doppler flowmetry perfusion probes were used to measure skin blood flow (expressed as cutaneous vascular conductance (CVC)). Skin surface cooling produced a significant reduction in CVC (P < 0.001) that persisted throughout the duration of the rewarming period. In addition, there was a hysteresis effect between CVC and skin temperature during the cooling and subsequent rewarming cycle (P < 0.01). Mixed model regression (MMR) showed a significant difference in the slopes of the CVC–skin temperature curves during cooling and rewarming (P < 0.001). Piecewise regression was used to investigate the temperature thresholds for acceleration of CVC during the cooling and rewarming periods. The two thresholds were shown to be significantly different (P = 0.003). The results show that localized cooling causes significant vasoconstriction that continues beyond the active cooling period despite skin temperatures returning toward baseline values. The significant and persistent reduction in skin perfusion may contribute to nonfreezing cold injury (NFCI) associated with cryotherapy. PMID:26632263
Cabrales, Pedro; Tsai, Amy G; Intaglietta, Marcos
Responses to exchange transfusion using red blood cells (RBCs) with modified hemoglobin (Hb) oxygen (O(2)) affinity were studied in the hamster window chamber model during acute anemia to determine its role on microvascular perfusion and tissue oxygenation. Allosteric effectors were introduced in the RBCs by electroporation. Inositol hexaphosphate (IHP) and 5-hydroxymethyl-2-furfural (5HMF) were used to decrease and increase Hb-O(2) affinity. In vitro P50s (partial pressure of O(2) at 50% Hb saturation) were modified to 10, 25, 45, and 50 mm Hg (normal P50 is 32 mm Hg). Allosteric effectors also decreased the Hill coefficient. Anemic condition was induced by isovolemic hemodilution exchanges using 6% dextran 70 kD to 18% hematocrit (Hct). Modified RBCs (at 18% Hct in 5% albumin solution) were infused by exchange transfusion of 35% of blood volume. Systemic parameters, microvascular perfusion, capillary perfusion (functional capillary density, FCD), and microvascular Po(2) levels were measured. RBcs with P50 of 45 mm Hg increased tissue Po(2) and decreased O(2) delivery (Do(2)) and extraction (Vo(2)) and RBCs with P50 of 60 mmHg reduced FCD, microvascular flow, tissue Po(2), Do(2) and Vo(2). Erythrocytes with increased Hb-O(2) affinity maintained hemodynamic conditions, Do(2) and decreased tissue Po(2). This study shows that in an anemic condition, maximal tissue Po(2) does not correspond to maximal Do(2) and Vo(2).
Zakharov, P.; Talary, M. S.; Caduff, A.
A dual-wavelength reflectance optical sensor for monitoring cutaneous blood perfusion is presented as a part of multisensor glucose monitoring system. A Monte-Carlo simulation of partial differential pathlengths has been used for the optimization of the distance from light source to detector. The simulation indicated that the light pathlength within the upper vascularised skin layers increases before reaching saturation at separation distances larger than 3 mm. Thus the sensor sensitivity does not benefit from larger source-detector distances. At the same time with a higher separation of the detector from the source, the intensity exponentially decreases while undesirable sensitivity to the muscle perfusion increases. The hardware prototype has been developed based on the simulation findings and tested in a laboratory setting and in a home use study by patients with diabetes. For both testing procedures the optical sensor demonstrated high sensitivity to perfusion changes. The effect of initial cutaneous blood increase under the sensor has been observed which can be associated with pressure-induced vasodilation as a response to the sensor application.
Viggiano, A; Manara, R; Conforti, R; Paccone, A; Secondulfo, C; Lorusso, L; Sbordone, L; Di Salle, F; Monda, M; Tedeschi, G; Esposito, F
Understanding mechanisms for vessel tone regulation within the trigeminal nuclei is of great interest because some headache syndromes are due to dysregulation of such mechanisms. Previous experiments on animal models suggest that mastication may alter neuron metabolism and blood supply in these nuclei. To investigate this hypothesis in humans, arterial spin-labeling magnetic resonance imaging (MRI) was used to measure blood perfusion within the principal trigeminal nucleus (Vp) and in the dorsolateral-midbrain (DM, including the mesencephalic trigeminal nucleus) in healthy volunteers, before and immediately after a mastication exercise consisting of chewing a gum on one side of the mouth for 1 h at 1 bite/s. The side preference for masticating was evaluated with a chewing test and the volume of the masseter muscle was measured on T1-weighted MRI scans. The results demonstrated that the mastication exercise caused a perfusion increase within the Vp, but not in the DM. This change was correlated to the preference score for the side where the exercise took place. Moreover, the basal Vp perfusion was correlated to the masseter volume. These results indicate that the local vascular tone of the trigeminal nuclei can be constitutively altered by the chewing practice and by strong or sustained chewing.
Richardson, J R; Ferguson, J; Hiscox, J; Rawles, J
BACKGROUND: Stroke distance, the systolic velocity integral of aortic blood flow, is a linear analogue of stroke volume; its product with heart rate is minute distance, analogous to cardiac output. OBJECTIVE: To investigate the feasibility of assessing cardiac output in children with a simple non-invasive Doppler ultrasound technique, and to determine the normal range of values. METHODS: Peak aortic blood velocity, stroke distance, and minute distance were measured through the suprasternal window in 166 children (mean age 9.6 years, range 2-14) using a portable non-imaging Doppler ultrasound instrument. RESULTS: The technique was well tolerated by all the children participating. Mean peak aortic blood velocity was 138 cm/s and was independent of age. Mean stroke distance was 31.8 cm and showed a small but significant increase with age; mean minute distance was 2490 cm and fell with age, as did heart rate. CONCLUSIONS: Suprasternal Doppler ultrasound measurement of stroke distance is a convenient, well tolerated, non-invasive technique for the assessment of cardiac output in children. The normal range of values during childhood has been established. The technique has great potential for assessing hypovolaemia in children. Images p307-a PMID:9785155
Elvira, L.; Sierra, C.; Galán, B.; Resa, P.
Non invasive techniques based on ultrasounds have advantageous features to study, characterize and monitor microbiological and enzymatic reactions. These processes may change the sound speed, viscosity or particle distribution size of the medium where they take place, which makes possible their analysis using ultrasonic techniques. In this work, two different systems for the analysis of microbiological liquid media based on ultrasounds are presented. In first place, an industrial application based on an ultrasonic monitoring technique for microbiological growth detection in milk is shown. Such a system may improve the quality control strategies in food production factories, being able to decrease the time required to detect possible contaminations in packed products. Secondly, a study about the growing of the Escherichia coli DH5 α in different conditions is presented. It is shown that the use of ultrasonic non invasive characterization techniques in combination with other conventional measurements like optical density provides complementary information about the metabolism of these bacteria.
Cohen-Ezra, Oranit; Ben-Ari, Ziv
Chronic liver diseases represent a major public health problem, accounting for significant morbidity and mortality worldwide. Prognosis and management of chronic liver diseases depend on the amount of liver fibrosis. Liver biopsy has long remained the gold standard for assessment of liver fibrosis. Liver biopsy is an invasive procedure with associated morbidity, it is rarely the cause for mortality, and has a few limitations. During the past two decades, in an attempt to overcome the limitations of liver biopsy, non-invasive methods for the evaluation of liver fibrosis have been developed, mainly in the field of viral hepatitis. This review will focus on different methods available for non-invasive evaluation of liver fibrosis including a biological approach which quantifies serum levels of biomarkers of fibrosis and physical techniques which measure liver stiffness by transient elastography, ultrasound or magnetic resonance based elastography, their accuracy, advantages and disadvantages.
Shah, Ashok; Hocini, Meleze; Haissaguerre, Michel; Jaïs, Pierre
Since more than 100 years, 12-lead electrocardiography (ECG) is the standard-of-care tool, which involves measuring electrical potentials from limited sites on the body surface to diagnose cardiac disorder, its possible mechanism, and the likely site of origin. Several decades of research has led to the development of a 252-lead ECG and computed tomography (CT) scan-based three-dimensional electro-imaging modality to non-invasively map abnormal cardiac rhythms including fibrillation. These maps provide guidance towards ablative therapy and thereby help advance the management of complex heart rhythm disorders. Here, we describe the clinical experience obtained using non-invasive technique in mapping the electrical disorder and guide the catheter ablation of atrial arrhythmias (premature atrial beat, atrial tachycardia, atrial fibrillation), ventricular arrhythmias (premature ventricular beats), and ventricular pre-excitation (Wolff-Parkinson-White syndrome).
Halim, A. A. A.; Laili, M. H.; Aziz, N. A.; Laili, A. R.; Salikin, M. S.; Rusop, M.
The aim of this review is to conduct a feasibility study of non-invasive evaluation in skeletal muscle oxygenation. This non-invasive evaluation could extract many information using a safe non-invasive method regarding to the oxygenation and microcirculation status in human blood muscle. This brief review highlights the progress of the application of NIRS to evaluate skeletal muscle oxygenation in various activity of human nature from the historical point of view to the present advancement. Since the discovery of non-invasive optical method during 1992, there are many non-invasive techniques uses optical properties on human subject such as near infrared spectroscopy NIRS, optical topography, functional near infrared spectroscopy fNIRS and imaging fNIRI. Furthermore, in this paper we discuss the light absorption potential (LAP) towards chromophores content inside human muscle. Modified beer lambert law was studied in order to build a better understanding toward LAP between chromophores under tissue multilayers in human muscle. This paper will describe the NIRS principle and the basis for its proposed used in skeletal muscle oxygenation. This will cover the advantages and limitation of such application. Thus, these non-invasive techniques could open other possibilities to study muscle performance diagnosis.
Cohen, Richard J.
It is critically important to be able to assess alterations in cardiovascular regulation during and after space flight. We propose to develop an instrument for the non-invasive assessment of such alterations that can be used on the ground and potentially during space flight. This instrumentation would be used by the Cardiovascular Alterations Team at multiple sites for the study of the effects of space flight on the cardiovascular system and the evaluation of countermeasures. In particular, the Cardiovascular Alterations Team will use this instrumentation in conjunction with ground-based human bed-rest studies and during application of acute stresses e.g., tilt, lower body negative pressure, and exercise. In future studies, the Cardiovascular Alterations Team anticipates using this instrumentation to study astronauts before and after space flight and ultimately, during space flight. The instrumentation may also be used by the Bone Demineralization/Calcium Metabolism Team, the Neurovestibular Team and the Human Performance Factors, Sleep and Chronobiology Team to measure changes in autonomic nervous function. The instrumentation will be based on a powerful new technology - cardiovascular system identification (CSI) - which has been developed in our laboratory. CSI provides a non-invasive approach for the study of alterations in cardiovascular regulation. This approach involves the analysis of second-to-second fluctuations in physiologic signals such as heart rate and non-invasively measured arterial blood pressure in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of multiple physiologic mechanisms, CSI provides a closed-loop model of the cardiovascular regulatory state in an individual subject.
Penn, R D; Walser, R; Kurtz, D; Ackerman, L
Computer and photographic methods for producing subtractions of computerized axial tomographic (CAT) scans have been developed. By subtracting point for point a normal scan from one taken after intravenous infusion of contrast material, a picture of the contrast in the cerebral vessels is created. By this method, tumor size and degree of vascularity may be assessed. Furthermore, abnormalities in perfusion and changes in blood volume due to mass effects and edema may be detected. Subtracting scans should add to the diagnostic potential of CAT and provide a noninvasive way to study vascular changes in cerebral disease.
Front, D.; Israel, O.; Joachims, H.; Brown, Y.; Eliachar, I.
A case report is presented of a woman with a tumor mass in the nasopharynx. Early and delayed scintigraphy with Technetium 99m-labeled RBCs showed a large area of increased uptake which was later shown to be a hemangioma by contrast angiography. The perfusion-blood pool mismatch observed in hemangiomas is characteristic of these lesions and has not been described in any other abnormalities. The Tc-RBC using both early and delayed scintigraphy is a simple, noninvasive method for assessing the vascular characteristics of these tumors. (JMT)
Hoscheidt, Siobhan M; Kellawan, J Mikhail; Berman, Sara E; Rivera-Rivera, Leonardo A; Krause, Rachel A; Oh, Jennifer M; Beeri, Michal S; Rowley, Howard A; Wieben, Oliver; Carlsson, Cynthia M; Asthana, Sanjay; Johnson, Sterling C; Schrage, William G; Bendlin, Barbara B
Insulin resistance (IR) is associated with poor cerebrovascular health and increased risk for dementia. Little is known about the unique effect of IR on both micro- and macrovascular flow particularly in midlife when interventions against dementia may be most effective. We examined the effect of IR as indexed by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) on cerebral blood flow in macro- and microvessels utilizing magnetic resonance imaging (MRI) among cognitively asymptomatic middle-aged individuals. We hypothesized that higher HOMA-IR would be associated with reduced flow in macrovessels and lower cortical perfusion. One hundred and twenty cognitively asymptomatic middle-aged adults (57 ± 5 yrs) underwent fasting blood draw, phase contrast-vastly undersampled isotropic projection reconstruction (PC VIPR) MRI, and arterial spin labeling (ASL) perfusion. Higher HOMA-IR was associated with lower arterial blood flow, particularly within the internal carotid arteries (ICAs), and lower cerebral perfusion in several brain regions including frontal and temporal lobe regions. Higher blood flow in bilateral ICAs predicted greater cortical perfusion in individuals with lower HOMA-IR, a relationship not observed among those with higher HOMA-IR. Findings provide novel evidence for an uncoupling of macrovascular blood flow and microvascular perfusion among individuals with higher IR in midlife.
Sallam, HN; Sallam, NH; Sallam, SH
Abstract With the widespread use of assisted reproduction, a simple and practical method for embryo selection is needed to optimize the chances of pregnancy while diminishing the incidence of multiple pregnancy and its accompanying problems. Many non-invasive methods for embryo selection have been proposed and some are more promising than others. This review summarizes these methods and attempts to evaluate them in the light of the best currently available evidence and to find out whether any of them is ripe for replacing or supplementing the time-honored method of morphological assessment. PMID:27909565
Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit
The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis.
Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M. Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit
The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis. PMID:25610249
Schmidl, Doreen; Garhofer, Gerhard; Schmetterer, Leopold
Glaucoma is an optic neuropathy of unknown origin. The most important risk factor for the disease is an increased intraocular pressure (IOP). Reducing IOP is associated with reduced progression in glaucoma. Several recent large scale trials have indicated that low ocular perfusion pressure (OPP) is a risk factor for the incidence, prevalence and progression of the disease. This is a strong indicator that vascular factors are involved in the pathogenesis of the disease, a hypothesis that was formulated 150 years ago. The relation between OPP and blood flow to the posterior pole of the eye is, however, complex, because of a phenomenon called autoregulation. Autoregulatory processes attempt to keep blood flow constant despite changes in OPP. Although autoregulation has been observed in many experiments in the ocular vasculature the mechanisms underlying the vasodilator and vasoconstrictor responses in face of changes in OPP remain largely unknown. There is, however, recent evidence that the human choroid regulates its blood flow better during changes in blood pressure induced by isometric exercise than during changes in IOP induced by a suction cup. This may have consequences for our understanding of glaucoma, because it indicates that blood flow regulation is strongly dependent not only on OPP, but also on the level of IOP itself. Indeed there is data indicating that reduction of IOP by pharmacological intervention improves optic nerve head blood flow regulation independently of an ocular vasodilator effect.
Tattersall, Glenn J
Infrared thermography is a non-invasive technique that measures mid to long-wave infrared radiation emanating from all objects and converts this to temperature. As an imaging technique, the value of modern infrared thermography is its ability to produce a digitized image or high speed video rendering a thermal map of the scene in false colour. Since temperature is an important environmental parameter influencing animal physiology and metabolic heat production an energetically expensive process, measuring temperature and energy exchange in animals is critical to understanding physiology, especially under field conditions. As a non-contact approach, infrared thermography provides a non-invasive complement to physiological data gathering. One caveat, however, is that only surface temperatures are measured, which guides much research to those thermal events occurring at the skin and insulating regions of the body. As an imaging technique, infrared thermal imaging is also subject to certain uncertainties that require physical modelling, which is typically done via built-in software approaches. Infrared thermal imaging has enabled different insights into the comparative physiology of phenomena ranging from thermogenesis, peripheral blood flow adjustments, evaporative cooling, and to respiratory physiology. In this review, I provide background and guidelines for the use of thermal imaging, primarily aimed at field physiologists and biologists interested in thermal biology. I also discuss some of the better known approaches and discoveries revealed from using thermal imaging with the objective of encouraging more quantitative assessment.
Thorling Thompson, Camilla; Wang, Haolu; Liu, Xin; Liang, Xiaowen; Crawford, Darrell H.; Roberts, Michael S.
Chronic liver disease causes 2,000 deaths in Australia per year and early diagnosis is crucial to avoid progression to cirrhosis and end stage liver disease. There is no ideal method to evaluate liver function. Blood tests and liver biopsies provide spot examinations and are unable to track changes in function quickly. Therefore better techniques are needed. Non-invasive imaging has the potential to extract increased information over a large sampling area, continuously tracking dynamic changes in liver function. This project aimed to study the ability of three imaging techniques, multiphoton and fluorescence lifetime imaging microscopy, infrared thermography and photoacoustic imaging, in measuring liver function. Collagen deposition was obvious in multiphoton and fluorescence lifetime imaging in fibrosis and cirrhosis and comparable to conventional histology. Infrared thermography revealed a significantly increased liver temperature in hepatocellular carcinoma. In addition, multiphoton and fluorescence lifetime imaging and photoacoustic imaging could both track uptake and excretion of indocyanine green in rat liver. These results prove that non-invasive imaging can extract crucial information about the liver continuously over time and has the potential to be translated into clinic in the assessment of liver disease.
Stauber, Hagit; Waisman, Dan; Sznitman, Josue; Technion-IIT Team; Department of Neonatology Carmel Medical Center; Faculty of Medicine-Technion IIT Collaboration
Microfluidic platforms are increasingly used to study blood microflows at true physiological scale due to their ability to overcome manufacturing obstacle of complex anatomical morphologies, such as the organ-specific architectures of the microcirculation. In the present work, we utilize microfluidic platforms to devise in vitro models of the underlying pulmonary capillary networks (PCN), where capillary lengths and diameters are similar to the size of RBCs (~ 5-10 μm). To better understand flow characteristics and dispersion of red blood cells (RBCs) in PCNs, we have designed microfluidic models of alveolar capillary beds inspired by the seminal ``sheet flow'' model of Fung and Sobin (1969). Our microfluidic PCNs feature confined arrays of staggered pillars with diameters of ~ 5,7 and 10 μm, mimicking the dense structure of pulmonary capillary meshes. The devices are perfused with suspensions of RBCs at varying hematocrit levels under different flow rates. Whole-field velocity patterns using micro-PIV and single-cell tracking using PTV are obtained with fluorescently-labelled RBCs and discussed. Our experiments deliver a real-scale quantitative description of RBC perfusion characteristics across the pulmonary capillary microcirculation.
Kandasamy, Kathirvel; Parthasarathi, Kaushik
The isolated blood-perfused lung preparation is widely used to visualize and define signaling in single microvessels. By coupling this preparation with real time imaging, it becomes feasible to determine permeability changes in individual pulmonary microvessels. Herein we describe steps to isolate rat lungs and perfuse them with autologous blood. Then, we outline steps to infuse fluorophores or agents via a microcatheter into a small lung region. Using these procedures described, we determined permeability increases in rat lung microvessels in response to infusions of bacterial lipopolysaccharide. The data revealed that lipopolysaccharide increased fluid leak across both venular and capillary microvessel segments. Thus, this method makes it possible to compare permeability responses among vascular segments and thus, define any heterogeneity in the response. While commonly used methods to define lung permeability require postprocessing of lung tissue samples, the use of real time imaging obviates this requirement as evident from the present method. Thus, the isolated lung preparation combined with real time imaging offers several advantages over traditional methods to determine lung microvascular permeability, yet is a straightforward method to develop and implement. PMID:25045895
IWASAKI, Masaki; JIN, Kazutaka; NAKASATO, Nobukazu; TOMINAGA, Teiji
Epilepsy surgery is aimed to remove the brain tissues that are indispensable for generating patient’s epileptic seizures. There are two purposes in the pre-operative evaluation: localization of the epileptogenic zone and localization of function. Surgery is planned to remove possible epileptogenic zone while preserving functional area. Since no single diagnostic modality is superior to others in identifying and localizing the epileptogenic zone, multiple non-invasive evaluations are performed to estimate the location of the epileptogenic zone after concordance between evaluations. Essential components of non-invasive pre-surgical evaluation of epilepsy include detailed clinical history, long-term video-electroencephalography monitoring, epilepsy-protocol magnetic resonance imaging (MRI), and neuropsychological testing. However, a significant portion of drug-resistant epilepsy is associated with no or subtle MRI lesions or with ambiguous electro-clinical signs. Additional evaluations including fluoro-deoxy glucose positron emission tomography (FDG-PET), magnetoencephalography and ictal single photon emission computed tomography can play critical roles in planning surgery. FDG-PET should be registered on three-dimensional MRI for better detection of focal cortical dysplasia. All diagnostic tools are complementary to each other in defining the epileptogenic zone, so that it is always important to reassess the data based on other results to pick up or confirm subtle abnormalities. PMID:27627857
Ma, Lina; Chuang, Chia-Chen; Weng, Weiliang; Zhao, Le; Zheng, Yongqiu; Zhang, Jinyan; Zuo, Li
No-reflow phenomenon, defined as inadequate perfusion of myocardium without evident artery obstruction, occurs at a high incidence after coronary revascularization. The mechanisms underlying no-reflow is only partially understood. It is commonly caused by the swelling of endothelial cells, neutrophil accumulation, and vasoconstriction, which are all related to acute inflammation. Persistent no-reflow can lead to hospitalization and mortality. However, an effective preventive intervention has not yet been established. We have previously found that paeonol, an active extraction from the root of Paeonia suffruticosa, can benefit the heart function by inhibiting tissue damage after ischemia, reducing inflammation, and inducing vasodilatation. To further investigate the potential cardioprotective action of paeonol on no-reflow, healthy male Wistar rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R) injury (left anterior descending coronary artery was ligated for 4 h followed by reperfusion for 8 h), and I/R injury pretreated with paeonol at two different doses. Real-time myocardial contrast echocardiography was used to monitor regional blood perfusion and cardiac functions. Our data indicated that paeonol treatment significantly reduces myocardial infarct area and no-reflow area (n = 8; p < 0.05). Regional myocardial perfusion (A·β) and cardiac functions such as ejection fraction, stroke volume, and fractional shortening were elevated by paeonol (n = 8; p < 0.05). Paeonol also lowered the serum levels of lactate dehydrogenase, creatine kinase, cardiac troponin T, and C-reactive protein, as indices of myocardial injury. Paeonol exerts beneficial effects on attenuating I/R-associated no-reflow injuries, and may be considered as a potential preventive treatment for cardiac diseases or post-coronary revascularization in which no-reflow often occurs. PMID:27493631
Raine-Fenning, N. J.; Ramnarine, K. V.; Nordin, N. M.; Campbell, B. K.
Three-dimensional (3D) power Doppler data is increasingly used to assess and quantify blood flow and tissue perfusion. The objective of this study was to assess the validity of common 3D power Doppler vascularity indices by quantification in well characterised in-vitro flow models. A computer driven gear pump was used to circulate a steady flow of a blood mimicking fluid through various well characterised flow phantoms to investigate the effect of the number of flow channels, flow rate, depth dependent tissue attenuation, blood mimic scatter particle concentration and ultrasound settings. 3D Power Doppler data were acquired with a Voluson 530D scanner and 7.5 MHz transvaginal transducer (GE Kretz). Virtual Organ Computer-aided Analysis software (VOCAL) was used to quantify the vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI). The vascular indices were affected by many factors, some intuitive and some with more complex or unexpected relationships (e.g. VI increased linearly with an increase in flow rate, blood mimic scatter particle concentration and number of flow channels, and had a complex dependence on pulse repetition frequency). Use of standardised settings and appropriate calibration are required in any attempt at relating vascularity indices with flow.
Fullana, J.-M.; Dispot, N.; Flaud, P.; Rossi, M.
A procedure is presented which allows to compute in a non-invasive manner, blood viscosity through flow measurements obtained at a fixed vessel cross-section. The data set is made of measurements (artery radius and spatially discrete velocity profiles) performed at given time intervals for which the signal to noise ratio is typical of U.S. Doppler velocimetry in clinical situation. This identification approach is based on the minimization, through a backpropagation algorithm, of a cost function quantifying the distance between numerical data obtained through Navier-Stokes simulations and experimental measurements. Since this cost function implicitly depends on the value of viscosity used in numerical simulations, its minimization determines an effective viscosity which is shown to be robust to measurement errors and sampling time. Such an approach is shown to work in an in vitro experiment, and seems to be suitable for in vivo measurements of viscosity by the atraumatic techniques of Doppler echography.
Vanstone, Meredith; King, Carol; de Vrijer, Barbra; Nisker, Jeff
New technologies analyzing fetal DNA in maternal blood have led to the wide commercial availability of non-invasive prenatal testing (NIPT). We present here for clinicians the ethical and policy issues related to an emerging practice option. Although NIPT presents opportunities for pregnant women, particularly women who are at increased risk of having a baby with an abnormality or who are otherwise likely to access invasive prenatal testing, NIPT brings significant ethics and policy challenges. The ethical issues include multiple aspects of informed decision-making, such as access to counselling about the possible results of the test in advance of making a decision about participation in NIPT. Policy considerations include issues related to offering and promoting a privately available medical strategy in publicly funded institutions. Ethics and policy considerations merge in NIPT with regard to sex selection and support for persons living with disabilities.
Henneman, Lidewij; Page-Chrisiaens, G C M L Lieve; Oepkes, Dick
The non-invasive prenatal test (NIPT) is an accurate and safe test in which blood from the pregnant woman is used to investigate if the unborn child possibly has trisomy 21 (Down's syndrome), trisomy 18 (Edwards' syndrome) or trisomy 13 (Patau syndrome). Since April 2014 the NIPT has been available in the Netherlands as part of the TRIDENT implementation project for those in whom the first trimester combined test showed an elevated risk (> 1:200) of trisomy, or on medical indication, as an alternative to chorionic villous sampling or amniocentesis. Since the introduction of the NIPT the use of these invasive tests, which are associated with a risk of miscarriage, has fallen steeply. The NIPT may replace the combined test. Also the number of conditions that is tested for can be increased. Modification of current prenatal screening will require extensive discussion, but whatever the modification, careful counseling remains essential to facilitate pregnant women's autonomous reproductive decision making.
Blatter, Cedric; Klein, Thomas; Grajciar, Branislav; Schmoll, Tilman; Wieser, Wolfgang; Andre, Raphael; Huber, Robert; Leitgeb, Rainer A.
Retinal and choroidal vascular imaging is an important diagnostic benefit for ocular diseases such as age-related macular degeneration. The current gold standard for vessel visualization is fluorescence angiography. We present a potential non-invasive alternative to image blood vessels based on functional Fourier domain optical coherence tomography (OCT). For OCT to compete with the field of view and resolution of angiography while maintaining motion artifacts to a minimum, ultrahigh-speed imaging has to be introduced. We employ Fourier domain mode locking swept source technology that offers high quality imaging at an A-scan rate of up to 1.68 MHz. We present retinal angiogram over ˜48 deg acquired in a few seconds in a single recording without the need of image stitching. OCT at 1060 nm allows for high penetration in the choroid and efficient separate characterization of the retinal and choroidal vascularization.
Malavasi, Silvia; Barone, Domenico; Gavelli, Giampaolo
Objectives. Tumour heterogeneity represents a key issue in CT perfusion (CTp), where all studies are usually based on global mean or median values of perfusion maps, often computed on whole tumour. We sought to determine whether, and to what extent, such global values can be representative of tumour heterogeneity, with respect to single slices, and could be used for therapy assessment. Materials and Methods. Twelve patients with one primary non-small cell lung cancer lesion were enrolled in this study, for a total amount of 26 CTp examinations and 118 slices. Mean and median blood flow (BF) values, calculated voxel-based, were computed on each slice and the whole tumour. To measure functional heterogeneity, entropy was calculated on BF values as well. Results. Most of the slices were not represented by the global BF values computed on the whole tumour. In addition, there are a number of lesions having equivalent global BF values, but they are composed of slices having very different heterogeneity distributions, that is, entropy values. Conclusions. Global mean/median BF values of the single slices separately should be considered for clinical assessment, only if interpreted through entropy computed on BF values. The numerical equivalence between global BF values of different lesions may correspond to different clinical status, thus inducing possible errors in choice of therapy when considering global values only. PMID:28164118
be determined by differential absorption spectroscopy using two wavelengths, 0/oSat- ga(, l)/p[a(X2)I [ Hielscher , et al., 1993; Haida and Chance...Biol 345:829-35, 1994. Hielscher AH, Tittel FK, and Jacques SL: Non-invasive monitoring of blood oxygenation by phase resolved transmission spectroscopy
Mayrovitz, H N; Groseclose, E E; Markov, M; Pilla, A A
Effects on skin blood perfusion of permanent ceramic magnets [0.1 T (1000 G) surface field], individually (disk shaped, 4 cm diameter x 1 cm thick) or in the form of a 11 x 7 in pad ( approximately 28 x 17.8 cm) with an array of 16 rectangular magnets (4.5 x 2.2 cm), were investigated in 16 female volunteers (27.4 +/- 1.7 years, range 21-48 years) using three separate protocols. In protocol A, a disk magnet was placed on the palmar surface of the hand in contact with the thenar eminence (n = 5). In protocol B, the magnet was placed on the hand dorsum overlying the thenar eminence (n = 5). In protocol C, the entire palm and fingers rested on the magnetic pad (n = 6). Magnets were in place for 36 min on one hand, and a sham was in place on the other hand. Blood perfusion was measured on the middle finger dorsum by laser Doppler flowmetry (LDF) and on the index finger by laser Doppler imaging (LDI). Perfusion measurements were simultaneously taken in sham and magnet exposed hands, before and during the entire magnet exposure interval. Magnetic field effects were tested by comparing skin blood perfusion sequences in magnet and sham exposed regions. Results showed no significant changes in either LDF or LDI perfusion at magnet or sham sites during exposure, nor were there any significant differences between sham and magnet sites for any protocol. Measurements of skin temperature at the LDF measurement sites also showed no significant change. It is concluded that in the healthy subjects studied with normal, unstressed circulation, magnets of the type and for the duration used, showed no detectible effect on skin blood perfusion in the anatomical area studied.
Durandy, Yves; Wang, Shigang; Ündar, Akif
Currently, only a small number of centrifugal pumps are being used for hemodynamic and/or respiratory support, but all of them have limitations. This article aims to present the Rhône-Poulenc 06 nonocclusive pressure-regulated blood pump. This pump was developed in France in the 1970s and used for decades in perfusion for cardiopulmonary bypass procedures, cardiac or lung assist as well as venovenous bypass during liver transplant. The intrinsic properties of this pump allowed us to describe a new technique for extracorporeal lung support in the 1980s, using a single cannula tidal flow venovenous bypass. This pump compared favorably with conventional pumps in terms of flow and pressure, hemolysis, pulsatility, safety, and cost-effectiveness. We believe that this simple pump could be an alternative to more sophisticated and expensive devices.
Caboot, Jason B.; Jawad, Abbas F.; McDonough, Joseph M.; Bowdre, Cheryl Y.; Arens, Raanan; Marcus, Carole L.; Mason, Thornton B.A.; Smith-Whitley, Kim; Ohene-Frempong, Kwaku; Allen, Julian L.
SUMMARY Assessment of oxyhemoglobin saturation in patients with sickle cell disease (SCD) is vital for prompt recognition of hypoxemia. The accuracy of pulse oximeter measurements of blood oxygenation in SCD patients is variable, partially due to carboxyhemoglobin (COHb) and methemoglobin (MetHb), which decrease the oxygen content of blood. This study evaluated the accuracy and reliability of a non-invasive pulse co-oximeter in measuring COHb and MetHb percentages (SpCO and SpMet) in children with SCD. We hypothesized that measurements of COHb and MetHb by non-invasive pulse co-oximetry agree within acceptable clinical accuracy with those made by invasive whole blood co-oximetry. Fifty children with SCD-SS underwent pulse co-oximetry and blood co-oximetry while breathing room air. Non-invasive COHb and MetHb readings were compared to the corresponding blood measurements. The pulse co-oximeter bias was 0.1% for COHb and −0.22% for MetHb. The precision of the measured SpCO was ±2.1% within a COHb range of 0.4–6.1%, and the precision of the measured SpMet was ±0.33% within a MetHb range of 0.1–1.1%. Non-invasive pulse co-oximetry was useful in measuring COHb and MetHb levels in children with SCD. Although the non-invasive technique slightly overestimated the invasive COHb measurements and slightly underestimated the invasive MetHb measurements, there was close agreement between the two methods. PMID:22328189
Chen, Lin; Zhan, Wei-Wei; Shen, Zhou-Jun; Rui, Wen-Bin; Lv, Chen; Chen, Man; Zhou, Jian-Qiao; Zhou, Ping; Zhou, Mi; Zhu, Ying
The changes of blood perfusion of contralateral testis after unilateral testicular torsion remain controversial. In this study, 28 New Zealand white male rabbits were randomly divided into five groups. Group A (n = 8), the control group, underwent a sham operation on the unilateral testis without inducing testicular torsion. In groups B, C, and D (n = 5 each), unilateral testicular torsion was induced, and, after 3, 6 or 24 h, respectively, detorsion was performed. In group E (n = 5), permanent unilateral testicular torsion was applied. Contrast-enhanced ultrasound was used to observe the blood perfusion of the contralateral testis at the following stages: pre-torsion (preopration), immediately post-torsion (postopration), pre-detorsion, immediately post-detorsion, and late-stage post-detorsion (6-12 h post-detorsion in groups B-D) or at a similar time point (15-21 h post-torsion in group E). Time-intensity curves were generated, and the following parameters were derived and analyzed: arrival time, time to peak intensity, peak intensity, and half-time of the descending peak intensity. The analysis revealed that blood perfusion of the contralateral testis increased immediately after testicular torsion on the opposite side (P < 0.05), which increased with prolonged testicular torsion of the other testis. This research demonstrated that contrast-enhanced ultrasound was valuable in evaluating blood perfusion of the contralateral testis after unilateral testicular torsion.
Amaddeo, Alessandro; Frapin, Annick; Fauroux, Brigitte
Use of long-term non-invasive ventilation is increasing exponentially worldwide in children of all ages. The treatment entails delivery of ventilatory assistance through a non-invasive interface. Indications for use of non-invasive ventilation include conditions that affect normal respiratory balance (eg, those associated with dysfunction of the central drive or respiratory muscles) and disorders characterised by an increase in respiratory load (eg, obstructive airway or lung diseases). The type of non-invasive ventilation used depends on the pathophysiological features of the respiratory failure. For example, non-invasive ventilation will need to either replace central drive if the disorder is characterised by an abnormal central drive or substitute for the respiratory muscles if the condition is associated with respiratory muscle weakness. Non-invasive ventilation might also need to unload the respiratory muscles in case of an increase in respiratory load, as seen in upper airway obstruction and some lung diseases. Technical aspects are also important when choosing non-invasive ventilation-eg, appropriate interface and device. The great heterogeneity of disorders, age ranges of affected children, prognoses, and outcomes of patients needing long-term non-invasive ventilation underline the need for management by skilled multidisciplinary centres with technical competence in paediatric non-invasive ventilation and expertise in sleep studies and therapeutic education.
Rajaram, Narasimhan; Reesor, Andrew F.; Mulvey, Christine S.; Frees, Amy E.; Ramanujam, Nirmala
We report the development of non-invasive, fiber-based diffuse optical spectroscopy for simultaneously quantifying vascular oxygenation (SO2) and glucose uptake in solid tumors in vivo. Glucose uptake was measured using a fluorescent glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG). Quantification of label-free SO2 and 2-NBDG-fluorescence-based glucose uptake 60 minutes after administration of the tracer (2-NBDG60) was performed using computational models of light-tissue interaction. This study was carried out on normal tissue and 4T1 and 4T07 murine mammary tumor xenografts in vivo. Injection of 2-NBDG did not cause a significant change in optical measurements of SO2, demonstrating its suitability as a functional reporter of tumor glucose uptake. Correction of measured 2-NBDG-fluorescence for the effects of absorption and scattering significantly improved contrast between tumor and normal tissue. The 4T1 and 4T07 tumors showed significantly decreased SO2, and 4T1 tumors demonstrated increased 2-NBDG60 compared with normal tissue (60 minutes after the administration of 2-NBDG when perfusion-mediated effects have cleared). 2-NBDG-fluorescence was found to be highly sensitive to food deprivation-induced reduction in blood glucose levels, demonstrating that this endpoint is indeed sensitive to glycolytic demand. 2-NBDG60 was also found to be linearly related to dose, underscoring the importance of calibrating for dose when comparing across animals or experiments. 4T1 tumors demonstrated an inverse relationship between 2-NBDG60 and SO2 that was consistent with the Pasteur effect, particularly when exposed to hypoxic gas breathing. Our results illustrate the potential of optical spectroscopy to provide valuable information about the metabolic status of tumors, with important implications for cancer prognosis. PMID:25635865
Förster, Alex; Mürle, Bettina; Böhme, Johannes; Al-Zghloul, Mansour; Kerl, Hans U; Wenz, Holger; Groden, Christoph
Although lacunar infarction accounts for approximately 25% of ischemic strokes, collateral blood flow through anastomoses is not well evaluated in lacunar infarction. In 111 lacunar infarction patients, we analyzed diffusion-weighted images, perfusion-weighted images, and blood flow on dynamic four-dimensional angiograms generated by use of Signal Processing In NMR-Software. Blood flow was classified as absent (type 1), from periphery to center (type 2), from center to periphery (type 3), and combination of type 2 and 3 (type 4). On diffusion-weighted images, lacunar infarction was found in the basal ganglia (11.7%), internal capsule (24.3%), corona radiata (30.6%), thalamus (24.3%), and brainstem (9.0%). In 58 (52.2%) patients, perfusion-weighted image showed a circumscribed hypoperfusion, in one (0.9%) a circumscribed hyperperfusion, whereas the remainder was normal. In 36 (62.1%) patients, a larger perfusion deficit (>7 mm) was observed. In these, blood flow was classified type 1 in four (11.1%), 2 in 17 (47.2%), 3 in 9 (25.0%), and 4 in six (16.7%) patients. Patients with lacunar infarction in the posterior circulation more often demonstrated blood flow type 2 and less often type 3 (p = 0.01). Detailed examination and graduation of blood flow in lacunar infarction by use of dynamic four-dimensional angiograms is feasible and may serve for a better characterization of this stroke subtype.
The paper, will present the most important non-invasive methods for diagnostic, in different fields of dentistry. Moreover, the laser-based methods will be emphasis. In orthodontics, 3D laser scanners are increasingly being used to establish database for normative population and cross-sectional growth changes but also to asses clinical outcomes in orthognatic surgical and non-surgical treatments. In prevention the main methods for diagnostic of demineralization and caries detection in early stages are represented by laser fluorescence - Quantitative Light Florescence (QLF); DiagnoDent-system-655nm; FOTI-Fiberoptic transillumination; DIFOTI-Digital Imaging Fiberoptic transillumination; and Optical Coherence Tomography (OCT). In odontology, Laser Doppler Flowmetry (LDF) is a noninvasive real time method used for determining the tooth vitality by monitoring the pulp microcirculation in traumatized teeth, fractured teeth, and teeth undergoing different conservative treatments. In periodontology, recently study shows the ability of LDF to evaluate the health of gingival tissue in periodontal tissue diseases but also after different periodontal treatments.
Kale, Ajit; Amende, Ivo; Piskorski, Katrina; Chu, Victor; Otero, Jose M; Mueller, Peter; Hampton, Thomas G
Linking gene defect to disease phenotypes in mice has become an essential step in the development of new drugs. Yet, many in vitro and in vivo assays require anaesthetic and surgery or do not reflect physiologically relevant phenomena. The effects of genes or diseases may only become apparent with stressors. Here, we apply non-invasive ECG monitoring and gait imaging systems to describe changes in the electrocardiogram and in gait dynamics resulting from a doubling of the ambulatory speed of mice. We found that B6C3H mice (n = 5) take 3.6 +/- 0.1 strides/second to walk 18cm/second and have a heart rate of 750 +/- 2bpm after 1 minute of walking at this speed. These mice significantly increase stride frequency to 5.2 +/- 0.1 strides/second in order to increase their speed to 36cm/second. The heart rate increased significantly (814 +/- 9bpm, p < 0.05) after trotting at the higher speed for 90 seconds, and the QRS interval duration significantly decreased (9.4 +/- 0.3ms vs. 10.4 +/- 0.3ms, p < 0.05). We discuss the application of the ECG screening and gait imaging systems to mouse models of Duchenne muscular dystrophy, Down syndrome and amyotrophic lateral sclerosis, diseases in humans that are known to affect the heart and neuromuscular systems.
Weatherly, Choyce A; Du, Siqi; Parpia, Curran; Santos, Polan T; Hartman, Adam L; Armstrong, Daniel W
The l-enantiomer is the predominant type of amino acid in all living systems. However, d-amino acids, once thought to be "unnatural", have been found to be indigenous even in mammalian systems and increasingly appear to be functioning in essential biological and neurological roles. Both d- and l-amino acid levels in the hippocampus, cortex, and blood samples from NIH Swiss mice are reported. Perfused brain tissues were analyzed for the first time, thereby eliminating artifacts due to endogenous blood, and decreased the mouse-to-mouse variability in amino acid levels. Total amino acid levels (l- plus d-enantiomers) in brain tissue are up to 10 times higher than in blood. However, all measured d-amino acid levels in brain tissue are typically ∼10 to 2000 times higher than blood levels. There was a 13% reduction in almost all measured d-amino acid levels in the cortex compared to those in the hippocampus. There is an approximate inverse relationship between the prevalence of an amino acid and the percentage of its d-enantiomeric form. Interestingly, glutamic acid, unlike all other amino acids, had no quantifiable level of its d-antipode. The bioneurological reason for the unique and conspicuous absence/removal of this d-amino acid is yet unknown. However, results suggest that d-glutamate metabolism is likely a unidirectional process and not a cycle, as per the l-glutamate/glutamine cycle. The results suggest that there might be unreported d-amino acid racemases in mammalian brains. The regulation and function of specific other d-amino acids are discussed.
Varadan, Vijay K.; Whitchurch, Ashwin K.; Saukesi, K.
Hypoglycemia - abnormal decrease in blood sugar - is a major obstacle in the management of diabetes and prevention of long-term complications, and it may impose serious effects on the brain, including impairment of memory and other cognitive functions. This paper presents the development of a non-invasive sensor with miniaturized telemetry device in a wrist-watch for monitoring glucose concentration in blood. The sensor concept is based on optical chiralit of glucose level in the interstitial fluid. The wrist watch consists of a laser power source of the wavelength compatible with the glucose. A nanofilm with specific chirality is placed at the bottom of the watch. The light then passes through the film and illuminates a small area on the skin.It has been documented that there is certain concentration of sugar level is taken by the intertitial fluid from the blood stream and deposit a portion of it at the dead skin. The wrist-watch when in contact with the outer skin of the human will thus monitor the glucose concentration. A wireless monitoring system in the watch then downloads the data from the watch to a Palm or laptop computer.
Kate, Mahesh P; Hansen, Mikkel B; Mouridsen, Kim; Østergaard, Leif; Choi, Victor; Gould, Bronwen E; McCourt, Rebecca; Hill, Michael D; Demchuk, Andrew M; Coutts, Shelagh B; Dowlatshahi, Dariush; Emery, Derek J; Buck, Brian H; Butcher, Kenneth S
Blood pressure (BP) reduction after intracerebral hemorrhage (ICH) is controversial, because of concerns that this may cause critical reductions in perihematoma perfusion and thereby precipitate tissue damage. We tested the hypothesis that BP reduction reduces perihematoma tissue oxygenation.Acute ICH patients were randomized to a systolic BP target of <150 or <180 mm Hg. Patients underwent CT perfusion (CTP) imaging 2 hours after randomization. Maps of cerebral blood flow (CBF), maximum oxygen extraction fraction (OEF(max)), and the resulting maximum cerebral metabolic rate of oxygen (CMRO2(max)) permitted by local hemodynamics, were calculated from raw CTP data.Sixty-five patients (median (interquartile range) age 70 (20)) were imaged at a median (interquartile range) time from onset to CTP of 9.8 (13.6) hours. Mean OEF(max) was elevated in the perihematoma region (0.44±0.12) relative to contralateral tissue (0.36±0.11; P<0.001). Perihematoma CMRO2(max) (3.40±1.67 mL/100 g per minute) was slightly lower relative to contralateral tissue (3.63±1.66 mL/100 g per minute; P=0.025). Despite a significant difference in systolic BP between the aggressive (140.5±18.7 mm Hg) and conservative (163.0±10.6 mm Hg; P<0.001) treatment groups, perihematoma CBF was unaffected (37.2±11.9 versus 35.8±9.6 mL/100 g per minute; P=0.307). Similarly, aggressive BP treatment did not affect perihematoma OEF(max) (0.43±0.12 versus 0.45±0.11; P=0.232) or CMRO2(max) (3.16±1.66 versus 3.68±1.85 mL/100 g per minute; P=0.857). Blood pressure reduction does not affect perihematoma oxygen delivery. These data support the safety of early aggressive BP treatment in ICH.
Adamson, R H; Clark, J F; Radeva, M; Kheirolomoom, A; Ferrara, K W; Curry, F E
Removal of plasma proteins from perfusates increases vascular permeability. The common interpretation of the action of albumin is that it forms part of the permeability barrier by electrostatic binding to the endothelial glycocalyx. We tested the alternate hypothesis that removal of perfusate albumin in rat venular microvessels decreased the availability of sphingosine-1-phosphate (S1P), which is normally carried in plasma bound to albumin and lipoproteins and is required to maintain stable baseline endothelial barriers (Am J Physiol Heart Circ Physiol 303: H825-H834, 2012). Red blood cells (RBCs) are a primary source of S1P in the normal circulation. We compared apparent albumin permeability coefficients [solute permeability (Ps)] measured using perfusates containing albumin (10 mg/ml, control) and conditioned by 20-min exposure to rat RBCs with Ps when test perfusates were in RBC-conditioned protein-free Ringer solution. The control perfusate S1P concentration (439 ± 46 nM) was near the normal plasma value at 37 °C and established a stable baseline Ps (0.9 ± 0.4 × 10(-6) cm/s). Ringer solution perfusate contained 52 ± 8 nM S1P and increased Ps more than 10-fold (16.1 ± 3.9 × 10(-6) cm/s). Consistent with albumin-dependent transport of S1P from RBCs, S1P concentrations in RBC-conditioned solutions decreased as albumin concentration, hematocrit, and temperature decreased. Protein-free Ringer solution perfusates that used liposomes instead of RBCs as flow markers failed to maintain normal permeability, reproducing the "albumin effect" in these mammalian microvessels. We conclude that the albumin effect depends on the action of albumin to facilitate the release and transport of S1P from RBCs that normally provide a significant amount of S1P to the endothelium.
Jia, Yali; Wang, Ruikang K
Alteration in regional cerebral blood flow (CBF) is the direct result of changes in neuronal activity. It is crucial to monitor the spatio-temporal characteristics of cerebro-vascular blood perfusion in the studies of cerebral diseases. Optical micro-angiography (OMAG) is a recently developed imaging technique capable of resolving 3D distribution of dynamic blood perfusion at a capillary level resolution within microcirculatory beds in vivo. The authors report the applications of OMAG in mouse ischemic stroke model. The study demonstrates that OMAG is a useful method capable of providing in vivo serial assessment of 3D cerebro-vascular pathophysiology with high sensitivity, and therefore, has the potential for use in the study of brain disorders and repairs.
The ability to determine the degree of cutaneous and subcutaneous tissue damage is essential for proper wound assessment and a significant factor for determining patient treatment and morbidity. Accurate characterization of tissue damage is critical for a number of medical applications including surgical removal of nonviable tissue, severity assessment of subcutaneous ulcers, and depth assessment of visually open wounds. The main objective of this research was to develop a non-invasive method for identifying the extent of tissue damage underneath intact skin that is not apparent upon visual examination. This work investigated the relationship between tissue optical properties, blood flow, and tissue viability by testing the hypotheses that (a) changes in tissue oxygenation and/or microcirculatory blood flow measurable by Diffuse Near Infrared Spectroscopy (DNIRS) and Diffuse Correlation Spectroscopy (DCS) differ between healthy and damaged tissue and (b) the magnitude of those changes differs for different degrees of tissue damage. This was accomplished by developing and validating a procedure for measuring microcirculatory blood flow and tissue oxygenation dynamics at multiple depths (up to 1 centimeter) using non-invasive DCS and DNIRS technologies. Due to the lack of pressure ulcer animal models that are compatible with our optical systems, a proof of concept was conducted in a porcine burn model prior to conducting clinical trials in order to assess the efficacy of the system in-vivo. A reduction in total hemoglobin was observed for superficial (5%) and deep burns (35%) along with a statistically significant difference between the optical properties of superficial and deep burns (p < 0.05). Burn depth and viable vessel density were estimated via histological samples. 42% of vessels in the dermal layer were viable for superficial burns, compared to 25% for deep burns. The differences detected in optical properties and hemoglobin content by optical measurements
Chia, Michael; Liao, Chin-An; Huang, Chih-Yang; Lee, Wen-Chih; Hou, Chien-Wen; Yu, Szu-Hsien; Harris, M Brennan; Hsu, Tung-Shiung; Lee, Shin-Da; Kuo, Chia-Hua
Swimmers tend to have greater body fat than athletes from other sports. The purpose of the study was to examine changes in body composition after altitude hypoxia exposure and the role of blood distribution to the skeletal muscle in swimmers. With a constant training volume of 12.3 km/day, young male swimmers (N = 10, 14.8 ± 0.5 years) moved from sea-level to a higher altitude of 2,300 meters. Body composition was measured before and after translocation to altitude using dual-energy X-ray absorptiometry (DXA) along with 8 control male subjects who resided at sea level for the same period of time. To determine the effects of hypoxia on muscle blood perfusion, total hemoglobin concentration (THC) was traced by near-infrared spectroscopy (NIRS) in the triceps and quadriceps muscles under glucose-ingested and insulin-secreted conditions during hypoxia exposure (16% O2) after training. While no change in body composition was found in the control group, subjects who trained at altitude had unequivocally decreased fat mass (-1.7 ± 0.3 kg, -11.4%) with increased lean mass (+0.8 ± 0.2 kg, +1.5%). Arterial oxygen saturation significantly decreased with increased plasma lactate during hypoxia recovery mimicking 2,300 meters at altitude (~93% versus ~97%). Intriguingly, hypoxia resulted in elevated muscle THC, and sympathetic nervous activities occurred in parallel with greater-percent oxygen saturation in both muscle groups. In conclusion, the present study provides evidence that increased blood distribution to the skeletal muscle under postprandial condition may contribute to the reciprocally increased muscle mass and decreased body mass after a 3-week altitude exposure in swimmers.
Higashi, S; Matsuda, H; Fujii, H; Ito, H; Yamashita, J
We report a case of luxury perfusion syndrome with temporary neurological deterioration after extracranial to intracranial bypass surgery. A preoperative computed tomographic scan showed no detectable infarct, and the measurement of regional cerebral blood flow showed severe depression of ipsilateral hemispheric perfusion. The patient developed temporary neurological deterioration after bypass surgery, with no recognizable pathological signs on postoperative computed tomographic and angiographic studies. Regional cerebral blood flow and volume were more elevated during the period of neurological deterioration than after the subsequent recovery. This strongly suggests that excessive blood flow directed into chronically ischemic brain through a graft may induce a luxury perfusion syndrome resulting in neurological deterioration.
Ware, Matthew J.; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A.; Corr, Stuart J.
Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30–40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors. PMID:28287120
Ware, Matthew J.; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A.; Corr, Stuart J.
Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30–40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.
Ware, Matthew J; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A; Corr, Stuart J
Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30-40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.
Wang, Jiongjiong; Rao, Hengyi; Wetmore, Gabriel S.; Furlan, Patricia M.; Korczykowski, Marc; Dinges, David F.; Detre, John A.
Despite the prevalence of stress in everyday life and its impact on happiness, health, and cognition, little is known about the neural substrate of the experience of everyday stress in humans. We use a quantitative and noninvasive neuroimaging technique, arterial spin-labeling perfusion MRI, to measure cerebral blood flow (CBF) changes associated with mild to moderate stress induced by a mental arithmetic task with performance monitoring. Elicitation of stress was verified by self-report of stress and emotional state and measures of heart rate and salivary-cortisol level. The change in CBF induced by the stress task was positively correlated with subjective stress rating in the ventral right prefrontal cortex (RPFC) and left insula/putamen area. The ventral RPFC along with right insula/putamen and anterior cingulate showed sustained activation after task completion in subjects reporting a high stress level during arithmetic tasks. Additionally, variations of baseline CBF in the ventral RPFC and right orbitofrontal cortex were found to correlate with changes in salivary-cortisol level and heart rate caused by undergoing stress tasks. We further demonstrated that the observed right prefrontal activation could not be attributed to increased cognitive demand accompanying stress tasks and extended beyond neural pathways associated with negative emotions. Our results provide neuroimaging evidence that psychological stress induces negative emotion and vigilance and that the ventral RPFC plays a key role in the central stress response. anterior cingulate cortex | arterial spin labeling | right prefrontal cortex
Rafiq, Aasma; Khanday, M A
Extreme environmental and physiological conditions present challenges for thermal processes in body tissues including multi-layered human eye. A mathematical model has been formulated in this direction to study the thermal behavior of the human eye in relation with the change in blood perfusion, porosity, evaporation and environmental temperatures. In this study, a comprehensive thermal analysis has been performed on the multi-layered eye using Pennes' bio-heat equation with appropriate boundary and interface conditions. The variational finite element method and MATLAB software were used for the solution purpose and simulation of the results. The thermoregulatory effect due to blood perfusion rate, porosity, ambient temperature and evaporation at various regions of human eye was illustrated mathematically and graphically. The main applications of this model are associated with the medical sciences while performing laser therapy and other thermoregulatory investigation on human eye.
Shim, Chi Young; Kim, Sajeevani; Chadderdon, Scott; Wu, Melinda; Qi, Yue; Xie, Aris; Alkayed, Nabil J.; Davidson, Brian P.
Skeletal muscle microvascular blood flow (MBF) increases in response to physiological hyperinsulinemia. This vascular action of insulin may facilitate glucose uptake. We hypothesized that epoxyeicosatrienoic acids (EETs), a family of arachadonic, acid-derived, endothelium-derived hyperpolarizing factors, are mediators of insulin's microvascular effects. Contrast-enhanced ultrasound (CEU) was performed to quantify skeletal muscle capillary blood volume (CBV) and MBF in wild-type and obese insulin-resistant (db/db) mice after administration of vehicle or trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid (t-AUCB), an inhibitor of soluble epoxide hydrolase that converts EETs to less active dihydroxyeicosatrienoic acids. Similar studies were performed in rats pretreated with l-NAME. CEU was also performed in rats undergoing a euglycemic hyperinsulinemic clamp, half of which were pretreated with the epoxygenase inhibitor MS-PPOH to inhibit EET synthesis. In both wild-type and db/db mice, intravenous t-AUCB produced an increase in CBV (65–100% increase at 30 min, P < 0.05) and in MBF. In db/db mice, t-AUCB also reduced plasma glucose by ∼15%. In rats pretreated with l-NAME, t-AUCB after produced a significant ≈20% increase in CBV, indicating a component of vascular response independent of nitric oxide (NO) production. Hyperinsulinemic clamp produced a time-dependent increase in MBF (19 ± 36 and 76 ± 49% at 90 min, P = 0.026) that was mediated in part by an increase in CBV. Insulin-mediated changes in both CBV and MBF during the clamp were blocked entirely by MS-PPOH. We conclude that EETs are a mediator of insulin-mediated augmentation in skeletal muscle perfusion and are involved in regulating changes in CBV during hyperinsulinemia. PMID:25336524
[The enhanced external counterpulsation as a method of non-invasive auxiliary blood circulation used for the combined rehabilitative treatment of the patients surviving after ischemic stroke (a review)].
Eneeva, M A; Kostenko, E V; Razumov, A N; Petrova, L V; Bobyreva, S N; Nesuk, O M
The present review of the foreign and domestic literature is concerned with the application of the method of enhanced external counterpulsation (EECP) therapy for the treatment of the patients presenting with various diseases. It is shown that many recent publications report extensive investigations of the clinical and neurophysiological aspects of the application of this method for the combined regenerative treatment of the patients surviving after ischemic stroke (IS). The possibility of the influence of EECP therapy on the system of regulation of the cerebral blood flow, the formation of collateral circulation in the ischemic tissue, and the cellular-humoral mechanisms are considered. It is concluded that the introduction of enhanced external counterpulsation therapy into the program of the combined rehabilitative treatment on an individual basis for the patients surviving after ischemic stroke is pathogenetically substantiated as promoting regression of clinical, neurological, and neuropsychological disorders.
Jonasson, Hanna; Fredriksson, Ingemar; Pettersson, Anders; Larsson, Marcus; Strömberg, Tomas
We have developed a new fiber-optic system that combines diffuse reflectance spectroscopy (DRS) and laser Doppler Flowmetry (LDF) for a multi-modal assessment of the microcirculation. Quantitative data is achieved with an inverse Monte Carlo algorithm based on an individually adaptive skin model. The output parameters are calculated from the model and given in absolute units: hemoglobin oxygen saturation (%), red blood cell (RBC) tissue fraction (%), and the speed resolved RBC perfusion separated into three speed regions; 0-1mm/s, 1-10mm/s and above 10mm/s (% mm/s). The aim was to explore microcirculatory parameters using the new optical method, integrating DRS and LDF in a joint skin model, during local heating of the dorsal foot and venous and arterial occlusion of the forearm in 23 healthy subjects (age 20-28years). There were differences in the three speed regions in regard to blood flow changes due to local heating, where perfusion for high speeds increased the most. There was also a high correlation between changes in oxygenation and changes in perfusion for higher speeds. Oxygen saturation at baseline was 44% on foot, increasing to 83% at plateau after heating. The larger increase in perfusion for higher speeds than for lower speeds together with the oxygenation increase during thermal provocation, shows a local thermoregulatory blood flow in presumably arteriolar dermal vessels. In conclusion, there are improved possibilities to assess microcirculation using integrated DRS and LDF in a joint skin model by enabling both oxygenation and speed resolved blood flow assessment simultaneously and in the same skin site. Output parameters in absolute units may also yield new insights about the microcirculatory system.
Rubin, D. N.; Thomas, J. D.
Myocardial perfusion imaging has long been a goal for the non-invasive echocardiographic assessment of the heart. However, many factors at play in perfusion imaging have made this goal elusive. Harmonic imaging and triggered imaging with newer contrast agents have made myocardial perfusion imaging potentially practical in the very near future. The application of indicator dilution theory to the coronary circulation and bubble contrast agents is fraught with complexities and sources of error. Therefore, quantification of myocardial perfusion by non-invasive echocardiographic imaging requires further investigation in order to make this technique clinically viable.
Wang, Ruikang K; Hurst, Sawan
Optical micro-angiography (OMAG) was developed to achieve volumetric imaging of the microstructures and dynamic cerebrovascular blood perfusion in mice with capillary level resolution and high signal-to-background ratio. In this paper, we present a high-speed and high-sensitivity OMAG imaging system by using an InGaAs line scan camera and broadband light source at 1.3 mum wavelength for enhanced imaging depth in tissue. We show that high quality imaging of cerebrovascular blood perfusion down to capillary level resolution with the intact skin and cranium are obtained in vivo with OMAG, without the interference from the blood perfusion in the overlaying skin. The results demonstrate the potential of 1.3 mum OMAG for high-speed and high-sensitivity imaging of blood perfusion in human and small animal studies.
Díaz Lobato, Salvador; Mayoralas Alises, Sagrario
The history of non-invasive mechanical ventilation goes back more than 100 years, but it was not until 1987 when what we could call "modern" non-invasive mechanical ventilation was developed. The description of Delaubier and Rideau of a patient with Duchenne's disease who had been effectively ventilated through a nasal mask marked the start of a new era in the history of non-invasive mechanical ventilation. Over these last 25years, we have witnessed exponential growth in its use, field of activity and technological advances on an exciting fast-paced track. We believe that it is time to review the main milestones that have marked the development of non-invasive mechanical ventilation to date, while paying homage to this therapeutic method that has contributed so much to the advancement of respiratory medicine in the last 25years.
Farrimond, Hannah R; Kelly, Susan E
Prenatal screening programmes have been critiqued for their routine implementation according to clinical rationale without public debate. A new approach, non-invasive prenatal diagnosis (NIPD), promises diagnosis of fetal genetic disorders from a sample of maternal blood without the miscarriage risk of current invasive prenatal tests (e.g. amniocentesis). Little research has investigated the attitudes of wider publics to NIPD. This study used Q-methodology, which combines factor analysis with qualitative comments, to identify four distinct "viewpoints" amongst 71 UK men and women: 1. NIPD as a new tool in the ongoing societal discrimination against the disabled; 2. NIPD as a positive clinical application offering peace of mind in pregnancy; 3. NIPD as a medical option justified for severe disorders only; and 4. NIPD as a valid expansion of personal choice. Concerns included the "trivialisation of testing" and the implications of commercial/direct-to-consumer tests. Q-methodology has considerable potential to identify viewpoints and frame public debate about new technologies.
Chiu, Han-Mo; Chang, Li-Chun; Hsu, Wen-Feng; Chou, Chu-Kuang; Wu, Ming-Shiang
There is an increasing trend of colorectal cancer incidence in Asia and nearly 45% of CRC cases worldwide occur in Asia therefore screening for CRC becomes an urgent task. Stool-based tests, including guaiac fecal occult blood test (gFOBT) and fecal immunochemical test (FIT), can select subjects at risk of significant colorectal neoplasms from the large target population thus are currently the most commonly used non-invasive screening tool in large population screening programs. FIT has the advantage over gFOBT in terms of higher sensitivity for early neoplasms, the ability to provide high-throughput automatic analysis, and better public acceptance thus greater effectiveness on reducing CRC mortality and incidence is expected. Owing to the large target population and constrained endoscopic capacity and manpower, FIT is nowadays the most popular CRC screening test in Asia. Some Asian countries have launched nationwide screening program in the past one or two decades but also encountered some challenges such as low screening participation rate, low verification rate after positive stool tests, low public awareness, and insufficient manpower. In addition, some controversial or potential future research issues are also addressed in this review.
Wang, Shutao; Kugelman, Tara; Buch, Amanda; Herman, Mathieu; Han, Yang; Karakatsani, Maria Eleni; Hussaini, S. Abid; Duff, Karen; Konofagou, Elisa E.
Optogenetics, a widely used technique in neuroscience research, is often limited by its invasive nature of application. Here, we present a noninvasive, ultrasound-based technique to introduce optogenetic channels into the brain by temporarily opening the blood-brain barrier (BBB). We demonstrate the efficiency of the method developed and evaluate the bioactivity of the non-invasively introduced channelrhodopsin channels by performing stimulation in freely behaving mice.
Wang, Shutao; Kugelman, Tara; Buch, Amanda; Herman, Mathieu; Han, Yang; Karakatsani, Maria Eleni; Hussaini, S. Abid; Duff, Karen; Konofagou, Elisa E.
Optogenetics, a widely used technique in neuroscience research, is often limited by its invasive nature of application. Here, we present a noninvasive, ultrasound-based technique to introduce optogenetic channels into the brain by temporarily opening the blood-brain barrier (BBB). We demonstrate the efficiency of the method developed and evaluate the bioactivity of the non-invasively introduced channelrhodopsin channels by performing stimulation in freely behaving mice. PMID:28059117
Thella, Ashok Kumar; Rizkalla, James; Helmy, Ahdy; Suryadevara, Vinay Kumar; Salama, Paul; Rizkalla, Maher
The existing modalities of bone diagnosis including X-ray and ultrasound may cite drawback in some cases related to health issues and penetration depth, while the ultrasound modality may lack image quality. Photo acoustic approach however, provides light energy to the acoustic wave, enabling it to activate and respond according to the propagating media (which is type of bones in this case). At the same time, a differential temperature change may result in the bio heat response, resulting from the heat absorbed across the multiple materials under study. In this work, we have demonstrated the features of using photo acoustic modality in order to non-invasively diagnose the type of human bones based on their electrical, thermal, and acoustic properties that differentiate the output response of each type. COMSOL software was utilized to combine both acoustic equations and bio heat equations, in order to study both the thermal and acoustic responses through which the differential diagnosis can be obtained. In this study, we solved both the acoustic equation and bio heat equations for four types of bones, bone (cancellous), bone (cortical), bone marrow (red), and bone marrow (yellow). 1 MHz acoustic source frequency was chosen and 10(5) W/m(2) power source was used in the simulation. The simulation tested the dynamic response of the wave over a distance of 5 cm from each side for the source. Near 2.4 cm was detected from simulation from each side of the source with a temperature change of within 0.5 K for various types of bones, citing a promising technique for a practical model to detect the type of bones via the differential temperature as well as the acoustic was response via the multiple materials associated with the human bones (skin and blood). The simulation results suggest that the PA technique may be applied to non-invasive diagnosis for the different types of bones, including cancerous bones. A practical model for detecting both the temperature change via
Federau, Christian; Hagmann, Patric; Maeder, Philippe; Müller, Markus; Meuli, Reto; Stuber, Matthias; O’Brien, Kieran
Measurement of microvascular perfusion with Intravoxel Incoherent Motion (IVIM) MRI is gaining interest. Yet, the physiological influences on the IVIM perfusion parameters (“pseudo-diffusion” coefficient D*, perfusion fraction f, and flow related parameter fD*) remain insufficiently characterized. In this article, we hypothesize that D* and fD*, which depend on blood speed, should vary during the cardiac cycle. We extended the IVIM model to include time dependence of D* = D*(t), and demonstrate in the healthy human brain that both parameters D* and fD* are significantly larger during systole than diastole, while the diffusion coefficient D and f do not vary significantly. The results non-invasively demonstrate the pulsatility of the brain’s microvasculature. PMID:24023649
Hudson, John M; Leung, Kogee; Burns, Peter N
Dynamic contrast enhanced ultrasound (DCE-US) is evolving as a promising tool to noninvasively quantify relative tissue perfusion in organs and solid tumours. Quantification using the method of disruption replenishment is best performed using a model that accurately describes the replenishment of microbubble contrast agents through the ultrasound imaging plane. In this study, the lognormal perfusion model was validated using an exposed in vivo rabbit kidney model. Compared against an implanted transit time flow meter, longitudinal relative flow measurement was (×3) less variable and correlated better when quantification was performed with the lognormal perfusion model (Spearman r = 0.90, 95% confidence interval [CI] = 0.05) vs. the prevailing mono-exponential model (Spearman r = 0.54, 95% CI = 0.18). Disruption-replenishment measurements using the lognormal perfusion model were reproducible in vivo to within 12%.
Huizar, Jose F; Warren, Mark D; Shvedko, Alexander G; Kalifa, Jérôme; Moreno, Javier; Mironov, Sergey; Jalife, José; Zaitsev, Alexey V
Changes in ventricular fibrillation (VF) organization occurring after the onset of global ischemia are relevant to defibrillation and survival but remain poorly understood. We hypothesized that ischemia-specific dynamic instability of the action potential (AP) causes a loss of spatiotemporal periodicity of propagation and broadening of the electrocardiogram (ECG) frequency spectrum during VF in the ischemic myocardium. We recorded voltage-sensitive fluorescence of di-4-ANEPPS (anterior left ventricle, 35 x 35 mm, 64 x 64 pixels) and the volume-conducted ECG in six blood-perfused hearts during 10 min of VF and global ischemia. We used coefficient of variation (CV) to estimate variability of AP amplitude, AP duration, and diastolic interval (CV-APA, CV-APD, and CV-DI, respectively). We computed excitation median frequency (Median_F), spectral width of the AP and ECG (SpW-AP and SpW-ECG, respectively), wavebreak incidence (WBI), and recurrence of propagation direction (RPD). We found three distinct phases of local VF dynamics: "relatively periodic" (
Atkins, H.L.; Oster, Z.H.; Anaise, D.; Wein, S.; Waltzer, W.; Gonder, A.; Cooch, E.; Rapaport, F.T.
The presently available non-invasive methods for the diagnosis of acute rejection crisis (ARC) of renal transplants are not satisfactory. However, the need for such a test is of paramount clinical importance. A prospective study of 74 post-transplantation events in renal allograft recipients was performed. Clinical, surgical exploration and biopsy data were correlated with TC-99m DTPA scintigraphy using the following indices: Global perfusion index (GPI), cortical perfusion index (CPI), medullary perfusion index (MPI), the peak-to-plateau ratio (P/P), iliac artery peak to renal peak time (delta-P) and washout half-time (T1/2). Of the 74 events, 24 were proven to be due to acute rejection crisis (ARC), 13 were of ureteral obstruction, 18 various nephropathies and 19 in stable renal transplant function. The P/P, delta-P and T1/2 were not good predictors of ARC; the sensitivity was 79%, 79% and 80% respectively. The sensitivity of the GPI was 58% and the specificity was 87%. The cortical perfusion index rated better: specificity=84% and sensitivity=87%. However, the best indicator of ARC seemed to be the percent increase in cortical perfusion index over previous values obtained during stable graft function. Thus the sensitivity was found to be 91% and specificity was 96%. The difference between global and cortical perfusion indices reflects shunting of blood for cortex to medulla. This study suggest that the cortical perfusion index (CPI) and the percent increase in CPI can be used to non-invasively diagnose acute renal allograft rejection.
Binzoni, Tiziano; Humeau-Heurtier, Anne; Abraham, Pierre; Mahe, Guillaume
Laser Doppler flowmetry (LDF) and laser speckle contrast imaging (LSCI) allow the monitoring of microvascular blood perfusion. The relationship between the measurements obtained by these two techniques remains unclear. In the present contribution, we demonstrate, experimentally and theoretically, that skin blood flow measurements obtained by LDF and LSCI techniques cannot be compared directly even after "classical" normalization procedure. This technical problem is generated by the nonlinear relationship existing between LDF and LSCI flow data. The experiments have been performed on five healthy voluntary subjects (forearm) by using repeated ischemia/reperfusion cycles to induce the necessary skin blood flow changes. LDF and LSCI data were simultaneously acquired on the same region of interest. Considering the importance of this problem from the clinical point of view, it is concluded that the definition of new corrected algorithms for LSCI is probably a mandatory step that must be taken into account if LDF and LSCI blood flow have to be compared.
Rationale and Design of the Dual Energy Computed Tomography for Ischemia Determination Compared to “Gold Standard” Non-invasive and Invasive Techniques (DECIDE-Gold): A Multicenter International Efficacy Diagnostic Study of Rest-Stress Dual-Energy Computed Tomography Angiography with Perfusion
Truong, Quynh A.; Knaapen, Paul; Pontone, Gianluca; Andreini, Daniele; Leipsic, Jonathon; Carrascosa, Patricia; Lu, Bin; Branch, Kelley; Raman, Subha; Bloom, Stephen; Min, James K.
BACKGROUND Dual-energy CT (DECT) has potential to improve myocardial perfusion for physiologic assessment of coronary artery disease (CAD). Diagnostic performance of rest-stress DECT perfusion (DECTP) is unknown. OBJECTIVE DECIDE-Gold is a prospective multicenter study to evaluate the accuracy of DECT to detect hemodynamic (HD) significant CAD, as compared to fractional flow reserve (FFR) as a reference standard. METHODS Eligible participants are subjects with symptoms of CAD referred for invasive coronary angiography (ICA). Participants will undergo DECTP, which will be performed by pharmacological stress, and participants will subsequently proceed to ICA and FFR. HD-significant CAD will be defined as FFR ≥ 0.80. In those undergoing myocardial stress imaging (MPI) by positron emission tomography (PET), single photon emission computed tomography (SPECT) or cardiac magnetic resonance (CMR) imaging, ischemia will be graded by % ischemic myocardium. Blinded core laboratory interpretation will be performed for CCTA, DECTP, MPI, ICA and FFR. RESULTS Primary endpoint is accuracy of DECTP to detect ≥ 1 HD-significant stenosis at the subject-level when compared to FFR. Secondary and tertiary endpoints are accuracies of combinations of DECTP at the subject and vessel levels compared to FFR and MPI. CONCLUSION DECIDE-Gold will determine the performance of DECTP for diagnosing ischemia. PMID:25549826
Gehrer, Simone; Pandey, Kamlesh V; Vaidya, Preyas J; Leuppi, Joerg D.; Tamm, Michael; Strobel, Werner
Introduction Nocturnal Non-invasive Positive Pressure Ventilation (NPPV) is the treatment of choice in patients with chronic hypercapnic respiratory failure due to hypoventilation. Continuous oxygen saturation measured with a pulse oximeter provides a surrogate measure of arterial oxygen saturation but does not completely reflect ventilation. Currently, Partial Pressure of Arterial (PaCO2) measured by arterial blood analysis is used for estimating the adequacy of ventilatory support and serves as the gold standard Aim To examine the safety, feasibility and utility of cutaneous capnography to re-titrate the non-invasive positive pressure ventilation settings in patients with chronic hypercapnic respiratory failure due to hypoventilation. Materials and Methods Twelve patients with chronic hypercapnic respiratory failure prospectively underwent complete polysomnography and cutaneous capnography measurement on the ear lobe. Non-invasive ventilation pressures were adjusted with the aim of normalizing cutaneous carbon dioxide or at least reducing it by 10 to 15 mmHg. Sensor drift for cutaneous carbon dioxide of 0.7 mmHg per hour was integrated in the analysis. Results Mean baseline cutaneous carbon dioxide was 45.4 ± 6.5 mmHg and drift corrected awake value was 45.1 ± 8.3 mmHg. The correlation of baseline cutaneous carbon dioxide and the corrected awake cutaneous carbon dioxide with arterial blood gas values were 0.91 and 0.85 respectively. Inspiratory positive airway pressures were changed in nine patients (75%) and expiratory positive airway pressures in eight patients (66%). Epworth sleepiness score before and after the study showed no change in five patients, improvement in six patients and deterioration in one patient. Conclusion Cutaneous capnography is feasible and permits the optimization of non-invasive ventilation pressure settings in patients with chronic hypercapnic respiratory failure due to hypoventilation. Continuous cutaneous capnography might serve as
Li, Chong-Hui; Chen, Yong-Wei; Chen, Yong-Liang; Yao, Li-Bin; Ge, Xin-Lan; Pan, Ke; Zhang, Ai-Qun; Dong, Jia-Hong
Hepatic ischaemia/reperfusion (I/R) injury is of primary concern during liver surgery. We propose a new approach for preserving low liver blood perfusion during hepatectomy either by occlusion of the portal vein (OPV) while preserving hepatic artery flow or occlusion of the hepatic artery while limiting portal vein (LPV) flow to reduce I/R injury. The effects of this approach on liver I/R injury were investigated. Rats were randomly assigned into 4 groups: sham operation, occlusion of the portal triad (OPT), OPV and LPV. The 7-day survival rate was significantly improved in the OPV and LPV groups compared with the OPT group. Microcirculatory liver blood flow recovered rapidly after reperfusion in the OPV and LPV groups but decreased further in the OPT group. The OPV and LPV groups also showed much lower ALT and AST levels, Suzuki scores, inflammatory gene expression levels, and parenchymal necrosis compared with the OPT group. An imbalance between the expression of vasoconstriction and vasodilation genes was observed in the OPT group but not in the OPV or LPV group. Therefore, preserving low liver blood perfusion by either the OPV or LPV methods during liver surgery is very effective for preventing hepatic microcirculatory dysfunction and hepatocyte injury.
Zhang, Xi; Jin, Lifang; Vlaisavljevich, Eli; Owens, Gabe E.; Gurm, Hitinder S.; Cain, Charles A.; Xu, Zhen
Histotripsy fractionates soft tissue by well-controlled acoustic cavitation using microsecond-long, high-intensity ultrasound pulses. The feasibility of using histotripsy as a non-invasive, drug-free, and image-guided thrombolysis method has been shown previously. A new histotripsy approach, termed Microtripsy, has recently been investigated for the thrombolysis application to improve treatment accuracy and avoid potential vessel damage. In this study, we investigated the effects of pulse repetition frequency (PRF) on microtripsy thrombolysis. Microtripsy thrombolysis treatments using different PRFs (5, 50, and 100 Hz) and doses (20, 50, and 100 pulses) were performed on blood clots in an in vitro vessel flow model. To quantitatively evaluate the microtripsy thrombolysis effect, the location of focal cavitation, the incident rate of pre-focal cavitation on the vessel wall, the size and location of the resulting flow channel, and the generated clot debris particles were measured. The results demonstrated that focal cavitation was always well-confined in the vessel lumen without contacting the vessel wall for all PRFs. Pre-focal cavitation on the front vessel wall was never observed at 5Hz PRF, but occasionally observed at PRFs of 50 Hz (1.2%) and 100 Hz (5.4%). However, the observed pre-focal cavitation was weak and didn’t significantly impact the focal cavitation. Results further demonstrated that, although the extent of clot fractionation per pulse was the highest at 5 Hz PRF at the beginning of treatment (<20 pulses), 100 Hz PRF generated the largest flow channels with a much shorter treatment time. Finally, results showed fewer large debris particles were generated at a higher PRF. Overall, the results of this study suggest that a higher PRF (50 or 100 Hz) may be a better choice for microtripsy thrombolysis to use clinically due to the larger resulting flow channel, shorter treatment time, and smaller debris particles. PMID:26670850
Zheng, J; Carr, J; Harris, K; Saker, M B; Cavagna, F M; Maggioni, F; Laub, G; Li, D; Finn, J P
Initial evaluation of a new blood pool agent, B-22956/1, for pulmonary imaging was performed in five domestic pigs with artificial embolism. Pre-embolism 3D pulmonary perfusion images were first acquired by injecting an extravascular agent, gadoteridol. The pulmonary arteries of the pigs were then occluded by the artificial emboli. Post-embolism perfusion scans were subsequently performed by injecting B-22956/1. Additional post-embolism high-spatial-resolution angiograms were also acquired. Parenchyma perfusion deficits were well depicted in the post-embolism perfusion maps. The post-embolism angiography clearly revealed the location and extent of the filling defects in the pulmonary vessels. Signal intensities of perfusion maps on the normal parenchyma were significantly improved (30%) by using B-22956/1, in comparison with perfusion images using gadoteridol (P < 0.01). Many pulmonary angiograms with approximately equal contrast could be obtained even at 22 minutes after the injection of B-22956/1. Our initial results indicate that blood pool agent B-22956/1 may provide opportunities for whole-lung-coverage perfusion mapping and additional high-resolution target angiograms after a single injection.
Shearman, C P; Gwynn, B R; Curran, F; Gannon, M X; Simms, M H
A method of non-invasive preoperative assessment of chronically ischaemic legs was developed that used clinical data and data derived from Doppler ultrasonography to produce a numerical score that could be compared with an angiographic score for stenosis of the popliteal artery trifurcation. The two scoring systems were applied retrospectively to 144 legs after femorodistal bypass. A close correlation was observed (r = 0.89, p less than 0.001), and both systems tended to predict the level of grafting undertaken. A prospective comparison was then made in 81 ischaemic legs that were examined by arteriography; the correlation between the two scoring systems remained close (r = 0.89, p less than 0.001), and the level of bypass was correctly predicted by the non-invasive assessment in 44 of 50 legs that were operated on. Use of the non-invasive assessment subsequently greatly reduced the indications for preoperative arteriography in patients requiring femorodistal vascular reconstruction. PMID:3094784
Tang, Fei; Wang, Xiaohao; Wang, Dongsheng; Li, Junfeng
A non-invasive glucose measurement system based on the method of metabolic heat conformation (MHC) is presented in this paper. This system consists of three temperature sensors, two humidity sensors, an infrared sensor and an optical measurement device. The glucose level can be deduced from the quantity of heat dissipation, blood flow rate of local tissue and degree of blood oxygen saturation. The methodology of the data process and the measurement error are also analyzed. The system is applied in a primary clinical test. Compared with the results of a commercial automated chemistry analyzer, the correlation coefficient of the collected data from the system is 0.856. Result shows that the correlation coefficient improves when the factor of heat dissipated by evaporation of the skin is added in. A non-invasive method of measuring the blood flow rate of local tissue by heat transmission between skin and contacted conductor is also introduced. Theoretical derivation and numerical simulation are completed as well. The so-called normalized difference mean (NDM) is chosen to express the quantity of the blood flow rate. The correlation coefficient between the blood flow rates by this method and the results of a Doppler blood flow meter is equal to 0.914.
Ibey, Bennett L.; Lee, Seungjoon; Ericson, M. Nance; Wilson, Mark A.; Cote, Gerard L.
A Multi-Layer Monte Carlo (MLMC) model was developed to predict the results of in vivo blood perfusion and oxygenation measurement of transplanted organs as measured by an indwelling optical sensor. A sensor has been developed which uses three-source excitation in the red and infrared ranges (660, 810, 940 nm). In vitro data was taken using this sensor by changing the oxygenation state of whole blood and passing it through a single-tube pump system wrapped in bovine liver tissue. The collected data showed that the red signal increased as blood oxygenation increased and infrared signal decreased. The center wavelength of 810 nanometers was shown to be quite indifferent to blood oxygenation change. A model was developed using MLMC code that sampled the wavelength range from 600-1000 nanometers every 6 nanometers. Using scattering and absorption data for blood and liver tissue within this wavelength range, a five-layer model was developed (tissue, clear tubing, blood, clear tubing, tissue). The theoretical data generated from this model was compared to the in vitro data and showed good correlation with changing blood oxygenation.
Timm, Ulrich; Kraitl, Jens; Schnurstein, Kirstin; Ewald, Hartmut
Hemoglobin (Hb) is an important component of red blood cells. The primary function of Hb is the transport of oxygen from the lungs to the tissue and carbon dioxide back to the lungs. The Hb concentration in human blood is an important parameter in evaluating the physiological status of an individual and an essential parameter in every blood count. Invasive methods are used to measure the Hb concentration, whereby blood is taken from the patient and subsequently analyzed. Apart from the discomfort of drawing blood samples, an added disadvantage of this method is the delay between the blood collection and its analysis, which does not allow real time patient monitoring in critical situations. A non-invasive method allows pain free continuous on-line patient monitoring with minimum risk of infection and facilitates real time data monitoring allowing immediate clinical reaction to the measured data.
Feltracco, Paolo; Serra, Eugenio; Barbieri, Stefania; Persona, Paolo; Rea, Federico; Loy, Monica; Ori, Carlo
Temporary graft dysfunction with gas exchange abnormalities is a common finding during the postoperative course of a lung transplant and is often determined by the post-reimplantation syndrome. Supportive measures including oxygen by mask, inotropes, diuretics, and pulmonary vasodilators are usually effective in non-severe post-reimplantation syndromes. However, in less-responsive clinical pictures, tracheal intubation with positive pressure ventilation, or non-invasive positive pressure ventilation (NIV), is necessary. We report on the clinical course of two patients suffering from refractory hypoxemia due to post-reimplantation syndrome treated with NIV in the prone and Trendelenburg positions. NIV was well tolerated and led to resolution of atelectactic areas and dishomogeneous lung infiltrates. Repeated turning from supine to prone under non invasive ventilation determined a stable improvement of gas exchange and prevented a more invasive approach. Even though NIV in the prone position has not yet entered into clinical practice, it could be an interesting option to achieve a better match between ventilation and perfusion. This technique, which we successfully applied in lung transplantation, can be easily extended to other lung diseases with non-recruitable dorso-basal areas.
Diffuse optical techniques were used to measure hemodynamics of tissues non-invasively. Spectroscopy and tomography of the brain, muscle and implanted tumors were carried out in animal models and humans. Two qualitatively different methods, diffuse optical tomography and diffuse correlation tomography, were hybridized permitting simultaneous measurement of total hemoglobin concentration, blood oxygen saturation and blood flow. This combination of information was processed further to derive estimates of oxygen metabolism (e.g. CMRO 2) in tissue. The diffuse correlation measurements of blood flow were demonstrated in human tissues, for the first time, demonstrating continous, non-invasive imaging of oxygen metabolism in large tissue volumes several centimeters below the tissue surface. The bulk of these investigations focussed on cerebral hemodynamics. Extensive validation of this methodology was carried out in in vivo rat brain models. Three dimensional images of deep tissue hemodynamics in middle cerebral artery occlusion and cortical spreading depression (CSD) were obtained. CSD hemodynamics were found to depend strongly on partial pressure of carbon dioxide. The technique was then adapted for measurement of human brain. All optical spectroscopic measurements of CMRO2 during functional activation were obtained through intact human skull non-invasively. Finally, a high spatio-temporal resolution measurement of cerebral blood flow due to somatosensory cortex activation following electrical forepaw stimulation in rats was carried out with laser speckle flowmetry. New analysis methods were introduced for laser speckle flowmetry. In other organs, deep tissue hemodynamics were measured on human calf muscle during exercise and cuff-ischemia and were shown to have some clinical utility for peripheral vascular disease. In mice tumor models, the measured hemodynamics were shown to be predictive of photodynamic therapy efficacy, again suggesting promise of clinical utility
Karmakar, Sanjit; Meyers, Ronald; Shih, Yanhua
The development of a non-invasive high resolving power quantum microscope would further advance progress in research and development in biomedical and biosciences as well as the field of medical technology. Longer wavelengths, i.e visible or near-infrared, provide less invasive impact. On the other hand shorter wavelengths, i.e. UV, can provide better resolving power. That is why the development of a non-invasive high resolving power quantum microscope is critical. In this article, we propose such a microscope by using two-color entangled photon ghost imaging technology.
Blesneag, A V; Popa, L; Stan, A D
The new tendency in rehabilitation involves non-invasive tools that, if applied early after stroke, promote neurorecovery. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation may correct the disruption of cortical excitability and effectively contribute to the restoration of movement and speech. The present paper analyses the results of non-invasive brain stimulation (NIBS) trials, highlighting different aspects related to the repetitive transcranial magnetic stimulation frequency, transcranial direct current stimulation polarity, the period and stimulation places in acute and subacute ischemic strokes. The risk of adverse events, the association with motor or language recovery specific training, and the cumulative positive effect evaluation are also discussed.
Chin, Jun L.; Pavlides, Michael; Moolla, Ahmad; Ryan, John D.
Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care. PMID:27378924
Itu, Lucian; Sharma, Puneet; Ralovich, Kristóf; Mihalef, Viorel; Ionasec, Razvan; Everett, Allen; Ringel, Richard; Kamen, Ali; Comaniciu, Dorin
We propose a CFD-based approach for the non-invasive hemodynamic assessment of pre- and post-operative coarctation of aorta (CoA) patients. Under our approach, the pressure gradient across the coarctation is determined from computational modeling based on physiological principles, medical imaging data, and routine non-invasive clinical measurements. The main constituents of our approach are a reduced-order model for computing blood flow in patient-specific aortic geometries, a parameter estimation procedure for determining patient-specific boundary conditions and vessel wall parameters from non-invasive measurements, and a comprehensive pressure-drop formulation coupled with the overall reduced-order model. The proposed CFD-based algorithm is fully automatic, requiring no iterative tuning procedures for matching the computed results to observed patient data, and requires approximately 6-8 min of computation time on a standard personal computer (Intel Core2 Duo CPU, 3.06 GHz), thus making it feasible for use in a clinical setting. The initial validation studies for the pressure-drop computations have been performed on four patient datasets with native or recurrent coarctation, by comparing the results with the invasively measured peak pressure gradients recorded during routine cardiac catheterization procedure. The preliminary results are promising, with a mean absolute error of less than 2 mmHg in all the patients.
Donati, Fabrizio; Figueroa, C. Alberto; Smith, Nicolas P.; Lamata, Pablo; Nordsletten, David A.
Pressure difference is an accepted clinical biomarker for cardiovascular disease conditions such as aortic coarctation. Currently, measurements of pressure differences in the clinic rely on invasive techniques (catheterization), prompting development of non-invasive estimates based on blood flow. In this work, we propose a non-invasive estimation procedure deriving pressure difference from the work-energy equation for a Newtonian fluid. Spatial and temporal convergence is demonstrated on in silico Phase Contrast Magnetic Resonance Image (PC-MRI) phantoms with steady and transient flow fields. The method is also tested on an image dataset generated in silico from a 3D patient-specific Computational Fluid Dynamics (CFD) simulation and finally evaluated on a cohort of 9 subjects. The performance is compared to existing approaches based on steady and unsteady Bernoulli formulations as well as the pressure Poisson equation. The new technique shows good accuracy, robustness to noise, and robustness to the image segmentation process, illustrating the potential of this approach for non-invasive pressure difference estimation. PMID:26409245
Gao, Lili; Li, Hanwei; Han, Jun; Zhang, Weihui
Introduction Preliminary data suggested that non-invasive methods could be useful to assess presence of oesophageal varices (OV) in liver cirrhosis. The primary objectives were to investigate non-invasive markers for diagnosing and grading OV in patients with primary biliary cirrhosis. Material and methods This study included a total of 106 consecutive treatment-naive patients with primary biliary cirrhosis (PBC). Results of physical examination, blood tests, and abdominal ultrasound scan (USS) were measured. Performance of non-invasive markers for OV was expressed as sensitivity, specificity, positive, and negative predictive values (PPV, NPV), accuracy, and area under the curve (AUC). Results Oesophageal varices were found in 54 (50.9%) and large OV in 28 of the 106 patients. Variables found to differ significantly between patients with any grade or large and without OV included increased spleen length, increased portal vein diameter, low platelet count, and low levels of albumin or low γ-glutamyltranspeptidase (γ-GTP) values. Area under the receiver operating characteristic curve showed that spleen length (cutoff = 156.0) had AUC 0.753 (95% CI: 0.657–0.849), and high NPV (82.1%) to exclude any grade OV. Large OV could be excluded with NPV 70.6% by spleen length. Conclusions Predictive risk factors that use readily available laboratory results and ultrasound scan results may reliably identify esophageal varices in patients with PBC. PMID:28261290
Robinson, Mark R.
An improved method and apparatus for determining noninvasively and in vivo one or more unknown values of a known characteristic, particularly the concentration of an analyte in human tissue. The method includes: (1) irradiating the tissue with infrared energy (400 nm-2400 nm) having at least several wavelengths in a given range of wavelengths so that there is differential absorption of at least some of the wavelengths by the tissue as a function of the wavelengths and the known characteristic, the differential absorption causeing intensity variations of the wavelengths incident from the tissue; (2) providing a first path through the tissue; (3) optimizing the first path for a first sub-region of the range of wavelengths to maximize the differential absorption by at least some of the wavelengths in the first sub-region; (4) providing a second path through the tissue; and (5) optimizing the second path for a second sub-region of the range, to maximize the differential absorption by at least some of the wavelengths in the second sub-region. In the preferred embodiment a third path through the tissue is provided for, which path is optimized for a third sub-region of the range. With this arrangement, spectral variations which are the result of tissue differences (e.g., melanin and temperature) can be reduced. At least one of the paths represents a partial transmission path through the tissue. This partial transmission path may pass through the nail of a finger once and, preferably, twice. Also included are apparatus for: (1) reducing the arterial pulsations within the tissue; and (2) maximizing the blood content i the tissue.
Konugolu Venkata Sekar, Sanathana; Pagliazzi, Marco; Negredo, Eugènia; Martelli, Fabrizio; Farina, Andrea; Dalla Mora, Alberto; Lindner, Claus; Farzam, Parisa; Pérez-Álvarez, Núria; Puig, Jordi; Taroni, Paola; Pifferi, Antonio; Durduran, Turgut
Non-invasive in vivo diffuse optical characterization of human bone opens a new possibility of diagnosing bone related pathologies. We present an in vivo characterization performed on seventeen healthy subjects at six different superficial bone locations: radius distal, radius proximal, ulna distal, ulna proximal, trochanter and calcaneus. A tailored diffuse optical protocol for high penetration depth combined with the rather superficial nature of considered tissues ensured the effective probing of the bone tissue. Measurements were performed using a broadband system for Time-Resolved Diffuse Optical Spectroscopy (TRS) to assess mean absorption and reduced scattering spectra in the 600-1200 nm range and Diffuse Correlation Spectroscopy (DCS) to monitor microvascular blood flow. Significant variations among tissue constituents were found between different locations; with radius distal rich of collagen, suggesting it as a prominent location for bone related measurements, and calcaneus bone having highest blood flow among the body locations being considered. By using TRS and DCS together, we are able to probe the perfusion and oxygen consumption of the tissue without any contrast agents. Therefore, we predict that these methods will be able to evaluate the impairment of the oxygen metabolism of the bone at the point-of-care.
Pagliazzi, Marco; Negredo, Eugènia; Martelli, Fabrizio; Farina, Andrea; Dalla Mora, Alberto; Lindner, Claus; Farzam, Parisa; Pérez-Álvarez, Núria; Puig, Jordi; Taroni, Paola; Pifferi, Antonio; Durduran, Turgut
Non-invasive in vivo diffuse optical characterization of human bone opens a new possibility of diagnosing bone related pathologies. We present an in vivo characterization performed on seventeen healthy subjects at six different superficial bone locations: radius distal, radius proximal, ulna distal, ulna proximal, trochanter and calcaneus. A tailored diffuse optical protocol for high penetration depth combined with the rather superficial nature of considered tissues ensured the effective probing of the bone tissue. Measurements were performed using a broadband system for Time-Resolved Diffuse Optical Spectroscopy (TRS) to assess mean absorption and reduced scattering spectra in the 600–1200 nm range and Diffuse Correlation Spectroscopy (DCS) to monitor microvascular blood flow. Significant variations among tissue constituents were found between different locations; with radius distal rich of collagen, suggesting it as a prominent location for bone related measurements, and calcaneus bone having highest blood flow among the body locations being considered. By using TRS and DCS together, we are able to probe the perfusion and oxygen consumption of the tissue without any contrast agents. Therefore, we predict that these methods will be able to evaluate the impairment of the oxygen metabolism of the bone at the point-of-care. PMID:27997565
Imms, Ryan; Hu, Sijung; Azorin-Peris, Vicente; Trico, Michaël.; Summers, Ron
Non-contact imaging photoplethysmography (PPG) is a recent development in the field of physiological data acquisition, currently undergoing a large amount of research to characterize and define the range of its capabilities. Contact-based PPG techniques have been broadly used in clinical scenarios for a number of years to obtain direct information about the degree of oxygen saturation for patients. With the advent of imaging techniques, there is strong potential to enable access to additional information such as multi-dimensional blood perfusion and saturation mapping. The further development of effective opto-physiological monitoring techniques is dependent upon novel modelling techniques coupled with improved sensor design and effective signal processing methodologies. The biometric signal and imaging processing platform (bSIPP) provides a comprehensive set of features for extraction and analysis of recorded iPPG data, enabling direct comparison with other biomedical diagnostic tools such as ECG and EEG. Additionally, utilizing information about the nature of tissue structure has enabled the generation of an engineering model describing the behaviour of light during its travel through the biological tissue. This enables the estimation of the relative oxygen saturation and blood perfusion in different layers of the tissue to be calculated, which has the potential to be a useful diagnostic tool.
Lambrecht, Richard M.; Packer, Samuel
There is described an apparatus and method for diagnosing ocular cancer that is both non-invasive and accurate which comprises two radiation detectors positioned before each of the patient's eyes which will measure the radiation level produced in each eye after the administration of a tumor-localizing radiopharmaceutical such as gallium-67.
Borchert, Mark S. (Inventor); Lambert, James L. (Inventor)
The invention provides a method of non-invasively determining intracranial pressure from measurements of an eye. A parameter of an optic nerve of the eye is determined, along with an intraocular pressure of the eye. The intracranial pressure may be determined from the intraocular pressure and the parameter.
Reeb-Sutherland, Bethany C.; Fox, Nathan A.
Eyeblink conditioning (EBC) is a classical conditioning paradigm typically used to study the underlying neural processes of learning and memory. EBC has a well-defined neural circuitry, is non-invasive, and can be employed in human infants shortly after birth making it an ideal tool to use in both developing and special populations. In addition,…
Non-invasive ventilation is an integral part of therapies used in patients presenting acute cardiogenic pulmonary oedema. In cardiac intensive care, these patients are treated by teams trained and practised in this technique. The nurses play a central role in the support and monitoring of the patients.
WANG, TING-TING; ZHOU, DONG
Focal cortical dysplasia (FCD) presents a strong clinical challenge especially for the treatment of the associated epilepsy. Epilepsy in FCD is often treatment-resistant and constitutes 50% of treatment-resistant cases. Antiepileptic drugs (AEDs) have been widely used in the treatment of FCD. However, evidence to suggest their specific effect on the treatment of FCD remains to be established. In view of this resistance, several alternative treatments have been suggested. Although treatment currently involves surgical management, non-invasive treatments have been identified. The aim of the present review, was to assess non-invasive management strategies including, i) mammalian target of rapamycin (mTOR) inhibitors, ii) ketogenic diet (KD), and iii) vagus nerve stimulation (VNS). In addition, we discussed the literature available regarding the use of AEDs in FCD. Experiments conducted with mammals detailing rapamycin gene mutations in FCD have produced vital information for exploring treatment options using mTOR inhibitors. Of note is the importance of KD in children with FCD. This diet has been shown to modify disease progression by attenuating chromatin modification, a master regulator for gene expression and functional adaptation of the cell. FCD has also been studied widely with neurostimulation techniques. The outcomes of these techniques have been found to be variable. For widespread dysplasias, VNS has been shown to produce responder rates of >50%. Nevertheless, non-invasive cranial nerve stimulation techniques such as transcutaneous VNS and non-invasive VNS are gaining better patient compatibility, albeit their efficacy remains to be established. PMID:27168769
Lambrecht, R.M.; Packer, S.
An apparatus and method is disclosed for diagnosing ocular cancer that is both non-invasive and accurate. The apparatus comprises two radiation detectors positioned before each of the patient's eyes which will measure the radiation level produced in each eye after the administration of a tumor-localizing radiopharmaceutical such as gallium-67. 2 figs.
Lambert, James L. (Inventor); Borchert, Mark S. (Inventor)
A non-invasive in vivo method for assessing macular carotenoids includes performing Optical Coherence Tomography (OCT) on a retina of a subject. A spatial representation of carotenoid levels in the macula based on data from the OCT of the retina can be generated.
Si, Biao; Luan, Zhao-Sheng; Wang, Tong-Jian; Ning, Yan-Song; Li, Na; Zhu, Meng; Liu, Zhong-Min; Ding, Guang-Hong; Qiao, Bin
The aim of the present study was to determine the distribution of lung blood in a modified bilateral Glenn procedure designed in our institute with lung perfusion scintigraphy. Sixteen consecutive patients who underwent modified bilateral Glenn operation from 2011 to 2014 were enrolled in the study. The control group consisted of 7 patients who underwent bidirectional Glenn shunt. Radionuclide lung perfusion scintigraphy was performed using Tc-99m-macro aggregated albumin (MAA) in all patients. For the patients in modified bilateral Glenn group, the time at which the radioactivity accumulation peaked did not differ significantly between the right and left lung field (t = 0.608, P = 0.554). The incidence of perfusion abnormality in each lung lobe also did not differ significantly (P = 0.426 by Fisher exact test). The radioactive counts were higher in the right lung than in the left lung, but the difference was not statistically significant (t = 1.502, P = 0.157). Radioactive perfusion in the lower lung field was significantly greater than that in the upper field (t = 4.368, P < 0.001). Compared with that in the bidirectional Glenn group, the ratio of radioactivity in the right lung to that in left lung was significantly lower in the modified bilateral Glenn group (t = 3.686, P = 0.002). Lung perfusion scintigraphy confirmed the benefit of the modified bilateral Glenn shunt with regard to more balanced blood perfusion in both lungs.
Wlodarczyk, Waldemar; Vlad, Julia; Lange, Thomas; Wust, Peter; Felix, Roland
The promising results, recently obtained in phantom experiments employing the MR-based proton resonance frequency (PRF) method as a non-invasive tool for the temperature monitoring of hyperthermia therapy, are not easily reproduced in vivo. One of the reasons is the impact of perfusion changes on the PRF-measured temperature. In our experiments in vivo, heat was supplied on one side of the volunteers knee or pelvis by a rubber hose with circulating warm water (50iC). The PRF method was calibrated by the constant temperature sensitivity of pure water of 0.011 ppm/iC. MR mapping of perfusion changes was based on T2*-weighted tracking of the first-pass kinetics of contrast agent. The hemodynamic parameters of regional blood volume (rBV) and mean transit time (MTT) were extracted by fitting pixel-by-pixel the first- pass kinetics to the gamma-variate model. Special attention was directed to improve a quality of the automatic non-linear fit at low signal-to-noise values. The distributions of PRF- based temperature changes show large areas of apparently high temperature elevations (exceeding 10iC) in regions close to the heat source, and others with just as large temperature decays in more distant regions. Areas of apparently high temperature elevations correlate with areas of blood flow increase and vice versa. In conclusion, the visible heat- induced PRF changes in vivo are primarily perfusion changes, which mask the much smaller true temperature changes.
Hu, Guo-Jie; Feng, Yu-Gong; Lu, Wen-Peng; Li, Huan-Ting; Xie, Hong-Wei; Li, Shi-Fang
OBJECTIVE Therapeutic neovascularization is a promising strategy for treating patients after an ischemic stroke; however, single-factor therapy has limitations. Stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) proteins synergistically promote angiogenesis. In this study, the authors assessed the effect of combined gene therapy with VEGF165 and SDF-1 in a rat model of cerebral infarction. METHODS An adenoviral vector expressing VEGF165 and SDF-1 connected via an internal ribosome entry site was constructed (Ad- VEGF165-SDF-1). A rat model of middle cerebral artery occlusion (MCAO) was established; either Ad- VEGF165-SDF-1 or control adenovirus Ad- LacZ was stereotactically microinjected into the lateral ventricle of 80 rats 24 hours after MCAO. Coexpression and distribution of VEGF165 and SDF-1 were examined by reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence. The neurological severity score of each rat was measured on Days 3, 7, 14, 21, and 28 after MCAO. Angiogenesis and vascular remodeling were evaluated via bromodeoxyuridine and CD34 immunofluorescence labeling. Relative cerebral infarction volumes were determined by T2-weighted MRI and triphenyltetrazolium chloride staining. Cerebral blood flow, relative cerebral blood volume, and relative mean transmit time were assessed using perfusion-weighted MRI. RESULTS The Ad- VEGF165-SDF-1 vector mediated coexpression of VEGF165 and SDF-1 in multiple sites around the ischemic core, including the cortex, corpus striatum, and hippocampal granular layer. Coexpression of VEGF165 and SDF-1 improved neural function, reduced cerebral infarction volume, increased microvascular density and promoted angiogenesis in the ischemic penumbra, and improved cerebral blood flow and perfusion. CONCLUSIONS Combined VEGF165 and SDF-1 gene therapy represents a potential strategy for improving vascular remodeling and recovery of neural function after cerebral
Muszak, J; Krzymowski, T; Gilun, P; Stefanczyk-Krzymowska, S
The objective of the current study was to check whether countercurrent transfer of dopamine occurs in the cavernous sinus of the rabbit and whether the rabbit can be used as an animal model to study cavernous sinus function. After exsanguination of the animal, oxygenated and warmed (37°C) Hanseneleit-Krebs buffer with autologous or homologous blood (in a 3:1 or 1:1 ratio) was pumped through both common carotid arteries into the head (60 ml/min; 80-100 mm Hg) and radiolabeled dopamine (3(H)-DA, 10 μCi) was infused into the cavernous sinus through the angular oculi vein. Cerebral blood from the basilar artery was collected from the cannulated vertebral artery during 3(H)-DA infusion and for 10 minutes after completion of infusion. Selected brain tissue samples were collected after completion of the head perfusion. It was demonstrated that dopamine can penetrate from the rabbit's cavernous sinus to the internal carotid artery supplying the brain. Dopamine permeation was greater when the rabbit head was perfused with buffer and blood in a 3:1 ratio than with 1:1 (P<0.01). When the head was perfused with buffer and blood in a 3:1 ratio, significant radioactivity was found in samples collected from the brain basilar artery during and after 3(H)-DA infusion (P<0.001). The radioactivity was identified as 34.13 ± 2.7% unmetabolized 3(H)-DA and 65.9 ± 2.7% its metabolites. Significant radioactivity was also found in some brain tissue samples in both groups (P<0.05). The concentration of free radiolabeled dopamine particles in the dialysate of blood plasma and plasma diluted with buffer did not differ significantly. Because the structures of the cavernous sinus and cavernous fragment of the internal carotid artery of the rabbit are similar to those in humans, it suggests that rabbits can serve as a model for experimental physiological studies of cavernous sinus function and retrograde dopamine transfer in the cavernous sinus should be considered as an important link in
Timm, Ulrich; Kraitl, Jens; Gewiss, Helge; Kamysek, Svend; Brock, Beate; Ewald, Hartmut
This paper will describe a novel multi-wavelength photometric method to measure carboxyhemoglobin (COHb) and methemoglobin (MetHb) concentration non-invasively. COHb and MetHb are so called dysfunctional hemoglobin derivatives and they are not able to carry oxygen. Standard pulse oximeters are only able to measure two derivatives, namely oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) but the presence of other derivatives in the blood may distort the readings. The paper presents a new approach of a noninvasive sensor system to measure COHb and MetHb and the validation in vivo and in vitro.
Disch, J; Maciel, F C; de Oliveira, M C; Orsini, M; Rabello, A
A polymerase chain reaction (PCR) assay for the detection of Leishmania spp. DNA in peripheral blood was optimized and evaluated for the diagnosis of human visceral leishmaniasis (VL) in Brazil during May 2001 to December 2002. Optimization of the technique resulted in a detection limit of 1.65 fg of purified L. (L.) chagasi DNA, equivalent to 1.65 x 10(-2) parasites. Leishmania DNA was detected in the blood of 48 of 53 patients with parasitologically-confirmed VL, which corresponds to a sensitivity of 91%. No DNA was detected in the peripheral blood of 15 healthy, non-exposed volunteers, giving a specificity of 100%. We conclude that detection of parasite DNA in peripheral blood offers a non-invasive, sensitive and rapid method for the detection of VL caused by L. (L.) chagasi.
Chen, Guangdong; Bian, Haiman; Jiang, Deguo; Cui, Mingwei; Ji, Shengzhang; Liu, Mei; Lang, Xu; Zhuo, Chuanjun
Many previous studies have reported that regional cerebral blood flow (rCBF) aberrations may be one of the pathological characteristics of depression and rCBF has demonstrated a certain degree of asymmetry. However, studies investigating the cerebral blood perfusion asymmetry changes of drug-naïve patients experiencing their first episode of major depression using pseudo-continuous arterial spin labeling (pCASL) are rare. Ten drug-naïve patients experiencing their first major depression episode and 15 healthy volunteers were enrolled in the current study. A novel pCASL method was applied to whole brain MRI scans of all of the samples. The Statistics Parameter Mapping and Relative Expression Software Tool software packages were used for the pre-processing and statistical analysis of the two sets of images, and the differences in the cerebral blood perfusion at the whole brain level were compared between the two groups. Compared with the healthy control group, the cerebral perfusion of the depression patients showed an asymmetric pattern. Decreased cerebral blood perfusion regions were primarily located in the left hemisphere, specifically in the left temporal lobe, frontal lobe and cingulate cortex [P<0.05 and cluster size ≥30 with false discovery rate (FDR) correction]. Simultaneously, increased perfusion regions were predominantly located in the right hemisphere, specifically in the right cerebellum, thalamus, frontal lobe and anterior cingulate cortex (P<0.05 and cluster size ≥30, with FDR correction). Thus, pCASL may characterize the alterations in cerebral blood perfusion of patients with depression. PMID:28101340
Jayanthy, A. K.; Sujatha, N.; Ramasubba Reddy, M.
An adequate amount of supply of blood to the body organs is essential for the optimum survival and function of the cells. The Red Blood Cells (RBC) which are the most abundant cells of the blood transports hemoglobin which in turn carries oxygen from the lungs to the tissues. And hence its concentration in blood is an important factor. In this paper, we are presenting LAser Speckle Contrast Analysis (LASCA) as a tool for analyzing RBC concentration. Preliminary results obtained using body fluid such as blood mimicking phantoms are presented here. The technique described provides a non-contact, non-scanning and whole field method for assessing RBC concentration non-invasively.
Kottmann, Jonas; Rey, Julien M.; Sigrist, Markus W.
Diabetes mellitus is a widespread metabolic disease without cure. Great efforts are being made to develop a non-invasive monitoring of the blood glucose level. Various attempts have been made, including a number of non-optical approaches as well as optical techniques involving visible, near- and mid-infrared light. However, no true breakthrough has been achieved so far, i.e., there is no fully non-invasive monitoring device available. Here we present a new study based on mid-infrared spectroscopy and photoacoustic detection. We employ two setups, one with a fiber-coupled photoacoustic (PA) cell and a tunable quantum cascade laser (QCL), and a second setup with two QCLs at different wavelengths combined with PA detection. In both cases, the PA cells are in direct skin contact. The performance is tested with an oral glucose tolerance test. While the first setup often gives reasonable qualitative agreement with ordinary invasive blood glucose measurements, the dual-wavelength approach yields a considerably improved stability and an uncertainty of only ±30 mg/dL of the blood glucose concentration level at a confidence level of 90%. This result is achieved without advanced data treatment such as principal component analysis involving extended wavelength ranges. PMID:27735878
Ansari, Rafat R.
As a 'window to the body', the eye offers the opportunity to use light in various forms to detect ocular and systemic abnormalities long before clinical symptoms appear and help develop preventative/therapeutic countermeasures early. The effects of space travel on human body are similar to those of normal aging. For example, radiation exposure in space could lead to formation of cataracts and cancer by damaging the DNA and causing gene mutation. Additionally, the zero-gravity environment causes fluid shifts in the upper extremities of the body and changes the way blood flows and organ system performs. Here on Earth, cataract, age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma are major eye diseases and are expected to double in next two decades. To detect, prevent, and treat untoward effects of prolonged space travel in real-time requires the development of non-invasive diagnostic technologies that are compact and powerful. We are developing fiber-optic sensors to evaluate the ocular tissues in health, aging, and disease employing the techniques of dynamic light scattering (cataract, uveitis, Alzheimer's, glaucoma, DR, radiation damage, refractive surgery outcomes), auto-fluorescence (aging, DR), laser-Doppler flowmetry (choroidal blood flow), Raman spectroscopy (AMD), polarimetry (diabetes), and retinal oximetry (occult blood loss). The non-invasive feature of these technologies integrated in a head-mounted/goggles-like device permits frequent repetition of tests, enabling evaluation of the results to therapy that may ultimately be useful in various telemedicine applications on Earth and in space.
Makaram, Prashanth; Owens, Dawn; Aceros, Juan
Blood glucose monitoring is considered the gold standard for diabetes diagnostics and self-monitoring. However, the underlying process is invasive and highly uncomfortable for patients. Furthermore, the process must be completed several times a day to successfully manage the disease, which greatly contributes to the massive need for non-invasive monitoring options. Human serums, such as saliva, sweat, breath, urine and tears, contain traces of glucose and are easily accessible. Therefore, they allow minimal to non-invasive glucose monitoring, making them attractive alternatives to blood measurements. Numerous developments regarding noninvasive glucose detection techniques have taken place over the years, but recently, they have gained recognition as viable alternatives, due to the advent of nanotechnology-based sensors. Such sensors are optimal for testing the amount of glucose in serums other than blood thanks to their enhanced sensitivity and selectivity ranges, in addition to their size and compatibility with electronic circuitry. These nanotechnology approaches are rapidly evolving, and new techniques are constantly emerging. Hence, this manuscript aims to review current and future nanomaterial-based technologies utilizing saliva, sweat, breath and tears as a diagnostic medium for diabetes monitoring. PMID:26852676
Makaram, Prashanth; Owens, Dawn; Aceros, Juan
Blood glucose monitoring is considered the gold standard for diabetes diagnostics and self-monitoring. However, the underlying process is invasive and highly uncomfortable for patients. Furthermore, the process must be completed several times a day to successfully manage the disease, which greatly contributes to the massive need for non-invasive monitoring options. Human serums, such as saliva, sweat, breath, urine and tears, contain traces of glucose and are easily accessible. Therefore, they allow minimal to non-invasive glucose monitoring, making them attractive alternatives to blood measurements. Numerous developments regarding noninvasive glucose detection techniques have taken place over the years, but recently, they have gained recognition as viable alternatives, due to the advent of nanotechnology-based sensors. Such sensors are optimal for testing the amount of glucose in serums other than blood thanks to their enhanced sensitivity and selectivity ranges, in addition to their size and compatibility with electronic circuitry. These nanotechnology approaches are rapidly evolving, and new techniques are constantly emerging. Hence, this manuscript aims to review current and future nanomaterial-based technologies utilizing saliva, sweat, breath and tears as a diagnostic medium for diabetes monitoring.
Maxwell, Adam D.; Cain, Charles A.; Duryea, Alexander P.; Yuan, Lingqian; Gurm, Hitinder S.; Xu, Zhen
Clinically available thrombolysis techniques are limited by either slow reperfusion (drugs) or invasiveness (catheters), and carry significant risks of bleeding. In this study, the feasibility of using histotripsy as an efficient and non-invasive thrombolysis technique was investigated. Histotripsy fractionates soft tissue through controlled cavitation using focused, short, high-intensity ultrasound pulses. In-vitro blood clots formed from fresh canine blood were treated by histotripsy. The treatment was applied using a focused 1-MHz transducer, with 5-cycle pulses at a pulse repetition rate of 1 kHz. Acoustic pressures varying from 2 – 12 MPa peak negative pressure were tested. Our results show that histotripsy can perform effective thrombolysis with ultrasound energy alone. Histotripsy thrombolysis only occurred at peak negative pressure ≥6 MPa when initiation of a cavitating bubble cloud was detected using acoustic backscatter monitoring. Blood clots weighing 330 mg were completely broken down by histotripsy in 1.5 – 5 minutes. The clot was fractionated to debris with >96% weight smaller than 5 μm diameter. Histotripsy thrombolysis treatment remained effective under a fast, pulsating flow (a circulatory model) as well as in static saline. Additionally, we observed that fluid flow generated by a cavitation cloud can attract, trap, and further break down clot fragments. This phenomenon may provide a non-invasive method to filter and eliminate hazardous emboli during thrombolysis. PMID:19854563
Debbage, P L; Sölder, E; Seidl, S; Hutzler, P; Hugl, B; Ofner, D; Kreczy, A
We previously applied intravital lectin perfusion in mouse models to elucidate mechanisms underlying vascular permeability. The present work transfers this technique to human models, analysing vascular permeability in macro- and microvessels. Human vascular endothelial surface carbohydrate biochemistry differs significantly from its murine counterpart, lacking alpha-galactosyl epitopes and expressing the L-fucose moiety in the glycocalyx; the poly-N-lactosamine glycan backbone is common to all mammals. We examined extensively lectin binding specificities in sections and in vivo, and then applied the poly-N-lactosamine-specific lectin LEA and the L-fucose-specific lectin UEA-I in human intravital perfusions. Transendothelial transport differed in macrovessels and microvessels. In microvessels of adult human fat tissue, rectal wall and rectal carcinomas, slow transendothelial transport by vesicles was followed by significant retention at the subendothelial basement membrane; paracellular passage was not observed. Passage time exceeded 1 h. Thus we found barrier mechanisms resembling those we described previously in murine tissues. In both adult and fetal macrovessels, the vena saphena magna and the umbilical vein, respectively, rapid passage across the endothelial lining was observed, the tracer localising completely in the subendothelial tissues within 15 min; vesicular transport was more rapid than in microvessels, and retention at the subendothelial basement membrane briefer.
Badiee, Parisa; Hashemizadeh, Zahra; Ramzi, Mani; Karimi, Mohammad; Mohammadi, Rasoul
Background Invasive fungal infection (IFIs) is a major infectious complication in immunocompromised patients. Early diagnosis and initiation of antifungal therapy is important to achieve the best outcome. Objectives The current study aimed to investigate the incidence of IFIs and evaluate the diagnostic performance of non-invasive laboratory tests: serologic (β-D-glucan, galactomannan) and molecular (nested polymerase chain reaction) tests to diagnose fungal infections in hematologic pediatric patients. Patients and Methods In a cross-sectional study from October 2014 to January 2015, 321 blood samples of 62 pediatric patients with hematologic disorders and at high risk for fungal infections were analyzed. Non-invasive tests including the Platelia Aspergillus enzyme immunoassay (EIA) to detect galactomannan antigen, Glucatell for β–D–glucan and nested PCR to detect Candida and Aspergillus species-specific DNA were used in a weekly screening strategy. Results Twenty six patients (42%) were considered as proven and probable IFIs, including 3 (5%) proven and 23 (37%) probable cases. Eighteen patients (29%) were considered as possible cases. The sensitivity, specificity, positive and negative predictive values for galactomannan test in 26 patients with proven and probable fungal infections were 94.4%, 100%, 100% and 94.7%; for β-D-glucan test 92.3%, 77.7%, 85%, 87.5% and for nested-PCR were 84.6%, 88.8%, 91.7% and 80%, respectively. Conclusions The rate of IFIs in pediatric patients with hematologic disorders is high, and sample collection from the sterile sites cannot be performed in immunocompromised patients. Detection of circulating fungal cell wall components and DNA in the blood using non-invasive methods can offer diagnostic help in patients with suspected IFIs. Their results should be interpreted in combination with clinical, radiological and microbiological findings. PMID:28138379
Boggione, Carolina Trucco; Luján Brajovich, Melina E.; Mattaloni, Stella M.; Di Mónaco, René A.; García Borrás, Silvia E.; Biondi, Claudia S.; Cotorruelo, Carlos M.
Background Non-invasive foetal RHD genotyping can predict haemolytic disease of the foetus and the newborn in pregnancies with anti-D alloantibodies and also avoid antenatal anti-D prophylaxis in pregnant women carrying an RHD negative foetus. Considering that the Argentine genetic background is the result of generations of intermixing between several ethnic groups, we evaluated the diagnostic performance of a non-invasive foetal RHD determination strategy to guide targeted antenatal RhD immunoprophylaxis. This algorithm is based on the analysis of four regions of the RHD gene in cell-free foetal DNA in maternal plasma and maternal and paternal RHD genotyping. Materials and methods DNA from 298 serologically D negative pregnant women between 19–28 weeks gestation were RHD genotyped. Foetal RHD status was determined by real-time PCR in 296 maternal plasma samples. In particular cases, RHDΨ and RHD-CE-Ds alleles were investigated in paternal DNA. Umbilical cord blood was collected at birth, and serological and molecular studies were performed. Results Of the 298 maternal samples, 288 were D−/RHD− and 10 D−/RHD+ (2 RHD*DAR; 5 RHD-CE-Ds; 3 RHDΨ). Plasma from RHD*DAR carriers was not analysed. Real-time PCR showed 210 RHD+ and 78 RHD− foetuses and 8 inconclusive results. In this latter group, paternal molecular studies were useful to report a RHD negative status in 5 foetuses while only 3 remained inconclusive. All the results, except one false positive due to a silent allele (RHD[581insG]), agreed with the neonatal typing performed in cord blood. Discussion The protocol used for non-invasive prenatal RHD genotyping proved to be suitable to determine foetal RHD status in our admixed population. The knowledge of the genetic background of the population under study and maternal and paternal molecular analysis can reduce the number of inconclusive results when investigating foetal RHD status. PMID:27136427
Juenemann, Martin; Goegel, Sinja; Obert, Martin; Schleicher, Nadine; Ritschel, Nouha; Doenges, Simone; Eitenmueller, Inka; Schwarz, Niko; Kastaun, Sabrina; Yeniguen, Mesut; Tschernatsch, Marlene; Gerriets, Tibo
Flat-panel volumetric computed tomography (fpVCT) is a non-invasive approach to three-dimensional small animal imaging. The capability of volumetric scanning and a high resolution in time and space enables whole organ perfusion studies. We aimed to assess feasibility and validity of fpVCT in cerebral perfusion measurement with impaired hemodynamics by evaluation of three well-established rat stroke models for temporary and permanent middle cerebral artery occlusion (MCAO). Male Wistar rats were randomly assigned to temporary (group I: suture model) and permanent (group II: suture model; III: macrosphere model) MCAO and to a control group. Perfusion scans with respect to cerebral blood flow (CBF) and volume (CBV) were performed 24h post intervention by fpVCT, using a Gantry rotation time of 1s and a total scanning time of 30s. Postmortem analysis included infarct-size calculation by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Infarct volumes did not differ significantly throughout intervention groups. After permanent MCAO, CBF significantly decreased in subcortical regions to 78.2% (group II, p=0.005) and 79.9% (group III, p=0.012) and in total hemisphere to 77.4% (group II, p=0.010) and 82.0% (group III, p=0.049). CBF was less impaired with temporary vessel occlusion. CBV measurement revealed no significant differences. Results demonstrate feasibility of cerebral perfusion quantification in rats with the fpVCT, which can be a useful tool for non-invasive dynamic imaging of cerebral perfusion in rodent stroke models. In addition to methodological advantages, CBF data confirm the macrosphere model as a useful alternative to the suture model for permanent experimental MCAO.
Vanegas, D. C.; Taguchi, M.; Chaturvedi, P.; Burrs, S.; McLamore, E. S.
Non-invasive tools that allow real-time quantification of molecules relevant to metabolism, homeostasis, and cell signaling in cells and tissue are of great importance for studying physiology. Several microsensor technologies have been developed to monitor concentration of molecules such as ions, oxygen, electroactive molecules (e.g., nitric oxide, hydrogen peroxide), and biomolecules (e.g., sugars, hormones). The major challenges for microsensors are overcoming relatively low sensitivity and low signal-to-noise ratio. Modern approaches for enhancing microsensor performance focus on the incorporation of catalytic nanomaterials to increase sensitivity, reduce response time, and increase operating range. To improve signal-to-noise ratio, a non-invasive microsensor modality called self-referencing (SR) is being applied. The SR technique allows measurement of temporal and spatial transport dynamics at the cell, tissue, organ, and organismal level.
Bhutiani, Neal; Grizzle, William E; Galandiuk, Susan; Otali, Denis; Dryden, Gerald W; Egilmez, Nejat K; McNally, Lacey R
Currently, several non-invasive modalities, including MRI and PET, are being investigated to identify early intestinal inflammation, longitudinally monitor disease status, or detect dysplastic changes in patients with inflammatory bowel disease (IBD). Here, we assess the applicability and utility of multispectral optoacoustic tomography (MSOT) in evaluating the presence and severity of colitis. Mice with bacterial colitis demonstrated a temporally associated increase in mesenteric and colonic vascularity with an increase in mean signal intensity of oxygenated hemoglobin (p=0.004) by MSOT two days after inoculation. These findings were significantly more prominent 7 days after inoculation, with increased mean signal intensity of oxygenated hemoglobin (p=0.0002) and the development of punctate vascular lesions on the colonic surface, which corresponded to changes observed on colonoscopy as well as histology. With improvements in depth of tissue penetration, MSOT may hold potential as a sensitive, accurate, non-invasive imaging tool in evaluation of patients with IBD.
Abbott, Rosalyn D.; Borowsky, Francis E.; Quinn, Kyle P.; Bernstein, David L.; Georgakoudi, Irene; Kaplan, David L.
Adipose tissue engineering is a diverse area of research where the developed tissues can be used to study normal adipose tissue functions, create disease models in vitro, and replace soft tissue defects in vivo. Increasing attention has been focused on the highly specialized metabolic pathways that regulate energy storage and release in adipose tissues which affect local and systemic outcomes. Non-invasive, dynamic measurement systems are useful to track these metabolic pathways in the same tissue model over time to evaluate long term cell growth, differentiation, and development within tissue engineering constructs. This approach reduces costs and time in comparison to more traditional destructive methods such as biochemical and immunochemistry assays and proteomics assessments. Towards this goal, this review will focus on important metabolic functions of adipose tissues and strategies to evaluate them with noninvasive in vitro methods. Current non-invasive methods, such as measuring key metabolic markers and endogenous contrast imaging will be explored. PMID:26399988
Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P.; Albadawi, Hassan; Felix Broelsch, G.; Watkins, Michael T.; Georgakoudi, Irene; Papisov, Mikhail; Mihm Jr., Martin C.; Austen Jr., William G.; Yarmush, Martin L.
Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases. PMID:25965851
Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P; Albadawi, Hassan; Felix Broelsch, G; Watkins, Michael T; Georgakoudi, Irene; Papisov, Mikhail; Mihm, Martin C; Austen, William G; Yarmush, Martin L
Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases.
Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P.; Albadawi, Hassan; Felix Broelsch, G.; Watkins, Michael T.; Georgakoudi, Irene; Papisov, Mikhail; Mihm, Martin C., Jr.; Austen, William G., Jr.; Yarmush, Martin L.
Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases.
Jette, B.D.; MacVicar, M.L.A. )
This paper reports on a SQUID magnetometer, employed as a highly sensitive ammeter, used to perform standard electroanalytic chemical measurements non- invasively. Specifically, the magnetic fields generated by the net ionic movement in the solution of a driven electrochemical system is detected by the gradiometer coils. The SQUID signal can then be compared to conventional current measurements. One such standard measurement investigated is Cyclic Voltametry (CV) which determines the I-V characteristics of an electrochemical system yielding critical kinetic parameters.
Leung, Jonathan Chung-Fai; Loong, Thomson Chi-Wang; Pang, James; Wei, Jeremy Lok; Wong, Vincent Wai-Sun
Portal hypertension is the central driver of complications in patients with chronic liver diseases and cirrhosis. The diagnosis of portal hypertension has important prognostic and clinical implications. In particular, screening for varices in patients with portal hypertension can effectively reduce the morbidity and mortality of variceal bleeding. In this article, we review the invasive and non-invasive methods to assess portal hypertension. Hepatic venous pressure gradient remains the gold standard to measure portal pressure but is invasive and seldom performed outside expert centers and research settings. In recent years, a number of non-invasive tests of fibrosis have shown good correlation with liver histology. They also show promise in identifying patients with portal hypertension and large varices. As a result, the latest Baveno VI consensus guidelines endorse the use of liver stiffness measurement by transient elastography and platelet count as initial assessment to select patients for varices screening. On the other hand, the performance of non-invasive tests in assessing the response to non-selective beta-blockers or transjugular intrahepatic portosystemic shunting is either suboptimal or unclear.
Chu, Victor; Otero, Jose M; Lopez, Orlando; Morgan, James P; Amende, Ivo; Hampton, Thomas G
Background The rapid increase in the development of mouse models is resulting in a growing demand for non-invasive physiological monitoring of large quantities of mice. Accordingly, we developed a new system for recording electrocardiograms (ECGs) in conscious mice without anesthesia or implants, and created Internet-accessible software for analyzing murine ECG signals. The system includes paw-sized conductive electrodes embedded in a platform configured to record ECGs when 3 single electrodes contact 3 paws. Results With this technique we demonstrated significantly reduced heart rate variability in neonates compared to adult mice. We also demonstrated that female mice exhibit significant ECG differences in comparison to age-matched males, both at baseline and in response to β-adrenergic stimulation. Conclusions The technology we developed enables non-invasive screening of large numbers of mice for ECG changes resulting from genetic, pharmacological, or pathophysiological alterations. Data we obtained non-invasively are not only consistent with what have been reported using invasive and expensive methods, but also demonstrate new findings regarding gender-dependent and age-dependent variations in ECGs in mice. PMID:11476671
Sharma, Suraj; Khalili, Korosh; Nguyen, Geoffrey Christopher
Liver cirrhosis is a common and growing public health problem globally. The diagnosis of cirrhosis portends an increased risk of morbidity and mortality. Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis. However, despite its universal use, liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks. In order to overcome the limitations of liver biopsy, a number of non-invasive techniques have been investigated for the assessment of cirrhosis. This review will focus on currently available non-invasive markers of cirrhosis. The evidence behind the use of these markers will be highlighted, along with an assessment of diagnostic accuracy and performance characteristics of each test. Non-invasive markers of cirrhosis can be radiologic or serum-based. Radiologic techniques based on ultrasound, magnetic resonance imaging and elastography have been used to assess liver fibrosis. Serum-based biomarkers of cirrhosis have also been developed. These are broadly classified into indirect and direct markers. Indirect biomarkers reflect liver function, which may decline with the onset of cirrhosis. Direct biomarkers, reflect extracellular matrix turnover, and include molecules involved in hepatic fibrogenesis. On the whole, radiologic and serum markers of fibrosis correlate well with biopsy scores, especially when excluding cirrhosis or excluding fibrosis. This feature is certainly clinically useful, and avoids liver biopsy in many cases.
Ring, M H; Rabensteiner, D F; Horwath-Winter, J; Boldin, I; Schrödl, F; Reitsamer, H; Haslwanter, T
Dry eye disease, or keratoconjunctivitis sicca, is a multifactorial syndrome with altered tear film homeostasis leading to ocular irritations. These alterations cause discomfort and stress for the patient, but only a few objective parameters allow for proper differential diagnosis into different subtypes of this condition. The mostly invasively performed standard assessment procedures for tear film diagnosis are manifold, but often correlate quite poorly with the subjectively reported symptoms. Due to the inherent limitations, e.g. the subjectivity of the commonly performed invasive tests, a number of devices have been developed to assess the human tear film non-invasively. Since the production, delivery, distribution and drainage of the tear film is a dynamic process, we have focused our review on non-invasive methods which are capable of continuous or repetitive observations of the tear film during an inter-blink interval. These dynamic methods include (1) Interferometry, (2) Pattern Projection, (3) Aberrometry, (4) Thermography; and (5) Evaporimetry. These techniques are discussed with respect to their diagnostic value, both for screening and differential diagnostic of Dry Eye Disease. Many of the parameters obtained from these tests have been shown to have the potential to reliably discriminate patients from healthy subjects, especially when the tests are performed automatically and objectively. The differentiation into subtypes based solely on a single, dynamic parameter may not be feasible, but the combination of non-invasively performed procedures may provide good discrimination results.
Williams, Monica; Lee, Jennifer K
Blood pressure can vary considerably during anesthesia. If blood pressure falls outside the limits of cerebrovascular autoregulation, children can become at risk of cerebral ischemic or hyperemic injury. However, the blood pressure limits of autoregulation are unclear in infants and children, and these limits can shift after brain injury. This article will review autoregulation, considerations for the hemodynamic management of children with brain injuries, and research on autoregulation monitoring techniques.
Allen, Patrick; Kang, Kyu-Tae; Bischoff, Joyce
We developed an in vivo vascularization model in which human endothelial colony-forming cells (ECFCs) and human mesenchymal progenitor cells (MPCs) form blood vessel networks when co-injected (ECFC + MPC) into nude mice in rat tail type I collagen, bovine fibrin or synthetic peptide PuraMatrix matrices. We used three approaches to determine the onset of functional vascularization when ECFC + MPC suspended in these matrices were implanted in vivo. The first was immunohistochemistry to detect vessels lined by human endothelial cells and filled with red blood cells. The second was in vivo vascular staining by tail vein injection of a mixture of Ulex europaeus agglutinin I (UEA-I), a lectin specific for human endothelium, and Griffonia simplicifolia isolectin B4 (GS-IB4 ), a lectin specific for rodent endothelium. The third approach employed contrast-enhanced ultrasound to measure the perfusion volumes of implants in individual animals over time. Human endothelial-lined tubular structures were detected in vivo on days 1 and 2 after implantation, with perfused human vessels detected on days 3 and 4. Contrast-enhanced ultrasound revealed significant perfusion of ECFC + MPC/collagen implants on days 1-4, at up to 14% perfused vascular volume. ECFC + MPC implanted in fibrin and PuraMatrix matrices also supported perfusion at day 1, as assessed by ultrasound (at 12% and 23% perfused vascular volume, respectively). This model demonstrates that ECFC + MPC suspended in any of the three matrices initiated a rapid onset of vascularization. We propose that ECFC + MPC delivered in vivo provide a means to achieve rapid perfusion of tissue-engineered organs or for in situ tissue repair.
Hynynen, K; DeYoung, D; Kundrat, M; Moros, E
The effect of blood perfusion rate on the temperature distribution during scanned, focused ultrasound hyperthermia was investigated using an in vivo dog kidney model. The results showed that the ultrasound beams could penetrate through the body wall without severe distortion, and that they could be used to induce controlled temperature elevations in the target volume. The blood perfusion rate of the heated tissue significantly modified the temperature distribution and the temperatures achieved in the kidney with no flow were about five times higher than in the case with full flow for the same applied acoustic power. It was also demonstrated that the power deposition pattern produced by scanned focused ultrasonic fields could be modified to give an acceptable temperature distribution in different perfusion situations. Similar trends were also obtained by using the bioheat transfer equation to simulate the experiment. Both the magnitude of the temperature elevations and the effect of perfusion on the temperature distributions obtained in the experiments were in agreement with the simulations. The main difference occurred at high perfusion rates where the experiments showed significant temperature elevation outside of the scanned volume and the simulation results predicted hardly any temperature increase 5 mm outside the scan. These observations indicate that both the theoretical power calculation programme and the temperature simulations will have value in the design of optimal heating systems, treatment planning and in the retrospective of the achieved temperature distributions.
Weber, Tobias; Ducos, Michel; Mulder, Edwin; Beijer, Åsa; Herrera, Frankyn; Zange, Jochen; Degens, Hans; Bloch, Wilhelm; Rittweger, Jörn
In the light of the dynamic nature of habitual plantar flexor activity, we utilized an incremental isokinetic exercise test (IIET) to assess the work-related power deficit (WoRPD) as a measure for exercise-induced muscle fatigue before and after prolonged calf muscle unloading and in relation to arterial blood flow and muscle perfusion. Eleven male subjects (31 ± 6 years) wore the HEPHAISTOS unloading orthosis unilaterally for 56 days. It allows habitual ambulation while greatly reducing plantar flexor activity and torque production. Endpoint measurements encompassed arterial blood flow, measured in the femoral artery using Doppler ultrasound, oxygenation of the soleus muscle assessed by near-infrared spectroscopy, lactate concentrations determined in capillary blood and muscle activity using soleus muscle surface electromyography. Furthermore, soleus muscle biopsies were taken to investigate morphological muscle changes. After the intervention, maximal isokinetic torque was reduced by 23·4 ± 8·2% (P<0·001) and soleus fibre size was reduced by 8·5 ± 13% (P = 0·016). However, WoRPD remained unaffected as indicated by an unchanged loss of relative plantar flexor power between pre- and postexperiments (P = 0·88). Blood flow, tissue oxygenation, lactate concentrations and EMG median frequency kinematics during the exercise test were comparable before and after the intervention, whereas the increase of RMS in response to IIET was less following the intervention (P = 0·03). In conclusion, following submaximal isokinetic muscle work exercise-induced muscle fatigue is unaffected after prolonged local muscle unloading. The observation that arterial blood flow was maintained may underlie the unchanged fatigability.
Xu, Feng; Ge, Yulin; Lu, Hanzhang
Cerebral metabolic rate of oxygen (CMRO2) is an important marker for brain function and brain health. Existing techniques for quantification of CMRO2 with Positron Emission Tomography (PET) or MRI involve special equipment and/or exogenous agent, and may not be suitable for routine clinical studies. In the present study, a non-invasive method is developed to estimate whole-brain CMRO2 in humans. This method applies phase-contrast MRI for quantitative blood flow measurement and T2-Relaxation-Under-Spin-Tagging (TRUST) MRI for venous oxygenation estimation, and uses the Fick principle of arteriovenous difference for the calculation of CMRO2. Whole-brain averaged CMRO2 values in young, healthy subjects were 132.1±20.0 μmol/100g/min, in good agreement with literature reports using PET. Various acquisition strategies for phase-contrast and TRUST MRI were compared, and it was found that non-gated phase-contrast and sagittal sinus TRUST MRI were able to provide the most efficient and accurate estimation of CMRO2. In addition, blood flow and venous oxygenation were found to be positively correlated across subjects. Owing to the non-invasive nature of this method, it may be a convenient and useful approach for assessment of brain metabolism in brain disorders as well as under various physiologic conditions. PMID:19353674
Shu, Ting; Zhang, Bob
Blood tests allow doctors to check for certain diseases and conditions. However, using a syringe to extract the blood can be deemed invasive, slightly painful, and its analysis time consuming. In this paper, we propose a new non-invasive system to detect the health status (Healthy or Diseased) of an individual based on facial block texture features extracted using the Gabor filter. Our system first uses a non-invasive capture device to collect facial images. Next, four facial blocks are located on these images to represent them. Afterwards, each facial block is convolved with a Gabor filter bank to calculate its texture value. Classification is finally performed using K-Nearest Neighbor and Support Vector Machines via a Library for Support Vector Machines (with four kernel functions). The system was tested on a dataset consisting of 100 Healthy and 100 Diseased (with 13 forms of illnesses) samples. Experimental results show that the proposed system can detect the health status with an accuracy of 93 %, a sensitivity of 94 %, a specificity of 92 %, using a combination of the Gabor filters and facial blocks.
Zheng, Zuci; Wang, Qiwen; Weng, Cuncheng; Lin, Xueliang; Lin, Yao; Feng, Shangyuan
An optical method of surface-enhanced Raman spectroscopy (SERS) was developed for non-invasive detection of hepatitis B surface virus (HBV). Hepatitis B virus surface antigen (HBsAg) is an established serological marker that is routinely used for the diagnosis of acute or chronic hepatitis B virus(HBV) infection. Utilizing SERS to analyze blood serum for detecting HBV has not been reported in previous literature. SERS measurements were performed on two groups of serum samples: one group for 50 HBV patients and the other group for 50 healthy volunteers. Blood serum samples are collected from healthy control subjects and patients diagnosed with HBV. Furthermore, principal components analysis (PCA) combined with linear discriminant analysis (LDA) were employed to differentiate HBV patients from healthy volunteer and achieved sensitivity of 80.0% and specificity of 74.0%. This exploratory work demonstrates that SERS serum analysis combined with PCA-LDA has tremendous potential for the non-invasive detection of HBV.
Jackson, M.; Smith, I.; King, M.; Shneerson, J.
BACKGROUND--Ventilatory failure is a well recognised complication of patients who have had a thoracoplasty for tuberculosis, but there are few data regarding the value of long term non-invasive assisted ventilation in this situation. METHODS--Thirty two patients who had had a thoracoplasty 20-46 years previously and who had developed respiratory failure were treated with nocturnal cuirass assisted ventilation or nasal positive pressure ventilation. Their survival and changes in arterial blood gases, nocturnal oximetry, and pulmonary function tests were assessed. RESULTS--The actuarial survival rates at one, three, five, and seven years after starting treatment were 91%, 74%, 64%, and 55%, respectively. Only seven of the 13 deaths were directly attributable to chronic respiratory or cardiac failure. The arterial PO2, PCO2, mean nocturnal oxygen saturation, vital capacity, and maximal inspiratory and expiratory pressures had all improved at the time of the initial post-treatment assessment (mean 12 days after starting treatment), but no subsequent improvements were seen after up to 48 months of follow up. Neither survival nor physiological improvements were correlated with the patients' age, the interval since thoracoplasty, or the pretreatment arterial blood gas tensions or results of pulmonary function tests. CONCLUSIONS--These results show that, even when ventilatory failure has developed, the prognosis with non-invasive assisted ventilation is good and the physiological abnormalities can be partially reversed. Patients who develop respiratory failure after a thoracoplasty should be considered for this type of long term domiciliary treatment. PMID:7940434
Orct, Tatjana; Jurasović, Jasna; Micek, Vedran; Karaica, Dean; Sabolić, Ivan
Concentrations of macro- and microelements in animal organs indicate the animal health status and represent reference data for animal experiments. Their levels in blood and tissues could be different between sexes, and could be different with and without blood in tissues. To test these hypotheses, in adult female and male rats the concentrations of various elements were measured in whole blood, blood plasma, and tissues from blood-containing (nonperfused) and blood-free liver, kidneys, and brain (perfused in vivo with an elements-free buffer). In these samples, 6 macroelements (Na, Mg, P, S, K, Ca) and 14 microelements (Fe, Mn, Co, Cu, Zn, Se, I, As, Cd, Hg, Pb, Li, B, Sr) were determined by inductively coupled plasma mass spectrometry following nitric acid digestion. In blood and plasma, female- or male-dominant sex differences were observed for 6 and 5 elements, respectively. In nonperfused organs, sex differences were observed for 3 (liver, brain) or 9 (kidneys) elements, whereas in perfused organs, similar differences were detected for 9 elements in the liver, 5 in the kidneys, and none in the brain. In females, perfused organs had significantly lower concentrations of 4, 5, and 2, and higher concentrations of 10, 4, and 7 elements, respectively, in the liver, kidneys, and brain. In males, perfusion caused lower concentrations of 4, 7, and 2, and higher concentrations of 1, 1, and 7 elements, respectively, in the liver, kidneys, and brain. Therefore, the residual blood in organs can significantly influence tissue concentrations of various elements and their sex-dependency.
Himori, N.; Taira, N.
1 The potency and selectivity of 5-(1-hydroxy-2-isopropylamino)butyl-8-hydroxy carbostyril hydrochloride hemihydrate (OPC-2009), a new β2-adrenoceptor stimulant, was compared with those of isoprenaline, trimetoquinol and salbutamol by the use of blood-perfused tracheal preparations in situ and of blood-perfused papillary muscle preparations of the dog. All drugs were injected intra-arterially. 2 All the four drugs decreased tracheal intraluminal pressure (tracheal relaxation) and increased tracheal blood flow in a dose-dependent manner. The four drugs produced a dose-dependent increase in developed tension of papillary muscles. In both preparations the duration of action of isoprenaline and salbutamol was short, whereas that of OPC-2009 and trimetoquinol was long. These effects were antagonized by propranolol. 3 Dose-response curves to the four drugs for tracheal relaxation were almost parallel. OPC-2009 was 2.4 times more potent, and trimetoquinol and salbutamol were 2.2 and 6.2 times less potent than isoprenaline in causing tracheal relaxation. 4 Dose-response curves to the four drugs for tracheal vasodilatation were also parallel. OPC-2009, trimetoquinol and salbutamol were 3.9, 6.7 and 23 times less potent than isoprenaline. 5 Slopes of the dose-response curves to the four drugs for increased developed tension were not parallel; that of OPC-2009 was the least steep, whereas that of isoprenaline was the steepest. Trimetoquinol, salbutamol and OPC-2009 were about 18, 570 and 2400 times less potent than isoprenaline. 6 Selectivity calculated from relative potencies indicate that OPC-2009 was about 6000 times, salbutamol about 92 times and trimetoquinol about 8.2 times more selective than isoprenaline for tracheal smooth muscle as compared to ventricular muscle. 7 The high potency and selectivity of OPC-2009 for tracheal smooth muscle and its long duration of action suggest its potential usefulness for treatment of bronchial asthma. 8 The present results are also
Fink, Christian; Ley, Sebastian; Puderbach, Michael; Plathow, Christian; Bock, Michael; Kauczor, Hans-Ulrich
The purpose of this study was to assess the feasibility of contrast-enhanced 3D perfusion MRI and MR angiography (MRA) of pulmonary embolism (PE) in pigs using a single injection of the blood pool contrast Gadomer. PE was induced in five domestic pigs by injection of autologous blood thrombi. Contrast-enhanced first-pass 3D perfusion MRI (TE/TR/FA: 1.0 ms/2.2 ms/40 degrees; voxel size: 1.3 x 2.5 x 4.0 mm3; TA: 1.8 s per data set) and high-resolution 3D MRA (TE/TR/FA: 1.4 ms/3.4 ms/40 degrees; voxel size: 0.8 x 1.0 x 1.6 mm3) was performed during and after a single injection of 0.1 mmol/kg body weight of Gadomer. Image data were compared to pre-embolism Gd-DTPA-enhanced MRI and post-embolism thin-section multislice CT (n = 2). SNR measurements were performed in the pulmonary arteries and lung. One animal died after induction of PE. In all other animals, perfusion MRI and MRA could be acquired after a single injection of Gadomer. At perfusion MRI, PE could be detected by typical wedge-shaped perfusion defects. While the visualization of central PE at MRA correlated well with the CT, peripheral PE were only visualized by CT. Gadomer achieved a higher peak SNR of the lungs compared to Gd-DTPA (21 +/- 8 vs. 13 +/- 3). Contrast-enhanced 3D perfusion MRI and MRA of PE can be combined using a single injection of the blood pool contrast agent Gadomer.
Stauffer, Paul R; Maccarini, Paolo F; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K; Bardati, Fernando; Tognolatti, Piero; Snow, Brent
BACKGROUND: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. METHODS: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. RESULTS: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. CONCLUSION: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects ≥2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.
Stauffer, Paul R.; Maccarini, Paolo F.; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K.; Bardati, Fernando; Tognolotti, Piero; Snow, Brent
Background: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. Methods: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. Results: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. Conclusion: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects >=2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.
Prudent, Michel; Stauber, Frédéric; Rapin, Alexis; Hallen, Sonia; Pham, Nicole; Abonnenc, Mélanie; Marvin, Laure; Rochat, Bertrand; Tissot, Jean-Daniel; Lion, Niels
To date, the development of bioreactors for the study of red blood cells (RBCs, daily transfused in the case of disease or hemorrhage) has focused on hematopoietic stem cells. Despite the fact that mature RBCs are enucleated and do not expand, they possess complex cellular and metabolic pathways, as well as post-translation modification signaling and gas-exchange regulation. In order to dynamically study the behavior of RBCs and their signaling pathways under various conditions, a small-scale perfusion bioreactor has been developed. The most advanced design developed here consists of a fluidized bed of 7.6 mL containing 3·109 cells and perfused at 8.5 μL/min. Mimicking RBC storage conditions in transfusion medicine, as a proof-of-concept, we investigated the ex vivo aging of RBCs under both aerobic and anaerobic conditions. Hence, RBCs stored in saline-adenine-glucose-mannitol (SAGM) were injected in parallel into two bioreactors and perfused with a modified SAGM solution over 14 days at room temperature under air or argon. The formation of a fluidized bed enabled easy sampling of the extracellular medium over the storage period used for the quantitation of glucose consumption and lactate production. Hemolysis and microvesiculation increased during aging and were reduced under anaerobic (argon) conditions, which is consistent with previously reported findings. Glucose and lactate levels showed expected trends, i.e., decreased and increased during the 2-week period, respectively; whereas extracellular glucose consumption was higher under aerobic conditions. Metabolomics showed depletion of glycolsis and pentose phosphate pathway metabolites, and an accumulation of purine metabolite end-products. This novel approach, which takes advantage of a fluidized bed of cells in comparison to traditional closed bags or tubes, does not require agitation and limit shear stress, and constantly segragates extracellular medium from RBCs. It thus gives access to several difficult
Habazettl, Helmut; Athanasopoulos, Dimitris; Kuebler, Wolfgang M; Wagner, Harrieth; Roussos, Charis; Wagner, Peter D; Ungruhe, Juergen; Zakynthinos, Spyros; Vogiatzis, Ioannis
Near-infrared spectroscopy (NIRS) with the tracer indocyanine green (ICG) may be used for measuring muscle blood flow (MBF) during exercise, if arterial ICG concentration is measured simultaneously. Although pulse dye densitometry allows for noninvasive measurement of arterial dye concentration, this technique is sensitive to motion and may not be applicable during exercise. The aim of this study was to evaluate a noninvasive blood flow index (BFI), which is derived solely from the muscle ICG concentration curve. In 10 male cyclists 5 mg ICG were injected into an antecubital vein at rest and during cycling at 30, 60, 70, 80, 90, and 100% of previously determined maximal work load. Simultaneously blood was withdrawn through a photodensitometer at 20 ml/min from the radial artery to measure arterial ICG concentration. To measure muscle tissue ICG concentrations, two sets of NIRS optodes were positioned on the skin, one over the left seventh intercostal space and the other over the left vastus lateralis muscle. MBF was calculated from the arterial and muscle concentration data according to Fick's principle. BFI was calculated solely from the muscle concentration curve as ICG concentration difference divided by rise time between 10 and 90% of peak. During exercise mean BFI values changed similarly to MBF in both intercostal and quadriceps muscles and showed excellent correlations with MBF: r = 0.98 and 0.96, respectively. Individual data showed some scattering among BFI and MBF values but still reasonable correlations of BFI with MBF: r = 0.73 and 0.72 for intercostal and quadriceps muscles, respectively. Interobserver variability, as analyzed by Bland-Altman plots, was considerably less for BFI than MBF. These data suggest that BFI can be used for measuring changes in muscle perfusion from rest to maximal exercise. Although absolute blood flow cannot be determined, BFI has the advantages of being essentially noninvasive and having low interobserver variability.
Edward, Kert; Farahi, Faramarz
Malaria is a virulent pathological condition which results in over a million annual deaths. The parasitic agent Plasmodium falciparum has been extensively studied in connection with this epidemic but much remains unknown about its development inside the red blood cell host. Optical and fluorescence imaging are among the two most common procedures for investigating infected erythrocytes but both require the introduction of exogenous contrast agents. In this letter, we present a procedure for the non-invasive in situ imaging of malaria infected red blood cells. The procedure is based on the utilization of simultaneously acquired quantitative phase and independent topography data to extract intracellular information. Our method allows for the identification of the developmental stages of the parasite and facilitates in situ analysis of the morphological changes associated with the progression of this disease. This information may assist in the development of efficacious treatment therapies for this condition.
In vivo neutron activation analysis, combined with gamma spectrometry, has ushered in a new era of clinical diagnosis and evaluation of therapies, as well as investigation into and modelling of body composition in both normal individuals and patients suffering from various diseases and dysfunctions. Body composition studies have provided baseline data on such vital constituents as nitrogen, potassium and calcium. The non-invasive measurement techniques are particularly suitable for study of the musculo-skeletal changes in body composition. Of particular relevance here is the measurement of calcium loss in astronauts during prolonged space flights.
Kubaski, Francyne; Tomatsu, Shunji; Patel, Pravin; Shimada, Tsutomu; Xie, Li; Yasuda, Eriko; Mason, Robert; Mackenzie, William G; Theroux, Mary; Bober, Michael B; Oldham, Helen M; Orii, Tadao; Shaffer, Thomas H
In clinical practice, respiratory function tests are difficult to perform in Morquio syndrome patients due to their characteristic skeletal dysplasia, small body size and lack of cooperation of young patients, where in some cases, conventional spirometry for pulmonary function is too challenging. To establish feasible clinical pulmonary endpoints and determine whether age impacts lung function in Morquio patients non-invasive pulmonary tests and conventional spirometry were evaluated. The non-invasive pulmonary tests: impulse oscillometry system, pneumotachography, and respiratory inductance plethysmography in conjunction with conventional spirometry were evaluated in twenty-two Morquio patients (18 Morquio A and 4 Morquio B) (7 males), ranging from 3 to 40 years of age. Twenty-two patients were compliant with non-invasive tests (100%) with the exception of IOS (81.8%-18 patients). Seventeen patients (77.3%) were compliant with spirometry testing. All subjects had normal vital signs at rest including >95% oxygen saturation, end tidal CO2 (38-44 mmHg), and age-appropriate heart rate (mean=98.3, standard deviation=19) (two patients were deviated). All patients preserved normal values in the impulse oscillometry system, pneumotachography, and respiratory inductance plethysmography, although predicted forced expiratory total (72.8±6.9 SE%) decreased with age and was below normal; phase angle (35.5±16.5°), %rib cage (41.6±12.7%), resonant frequency, and forced expiratory volume in 1 s/forced expiratory volume total (110.0±3.2 SE%) were normal and not significantly impacted by age. The proposed non-invasive pulmonary function tests are able to cover a greater number of patients (young patients and/or wheel-chair bound), thus providing a new diagnostic approach for the assessment of lung function in Morquio syndrome which in many cases may be difficult to evaluate. Morquio patients studied herein demonstrated no clinical or functional signs of restrictive and
Suryadevara, N K; Mukhopadhyay, S C; Barrack, L
In this article, a smart wireless sensing non-invasive system for estimating the amount of fluid loss, a person experiences while physical activity is presented. The system measures three external body parameters, Heart Rate, Galvanic Skin Response (GSR, or skin conductance), and Skin Temperature. These three parameters are entered into an empirically derived formula along with the user's body mass index, and estimation for the amount of fluid lost is determined. The core benefit of the developed system is the affluence usage in combining with smart home monitoring systems to care elderly people in ambient assisted living environments as well in automobiles to monitor the body parameters of a motorist.
Cui, Han; Chen, Yi; Zhong, Weizheng; Yu, Haibo; Li, Zhifeng; He, Yuhai; Yu, Wenlong; Jin, Lei
Bell's palsy is a kind of peripheral neural disease that cause abrupt onset of unilateral facial weakness. In the pathologic study, it was evidenced that ischemia of facial nerve at the affected side of face existed in Bell's palsy patients. Since the direction of facial nerve blood flow is primarily proximal to distal, facial skin microcirculation would also be affected after the onset of Bell's palsy. Therefore, monitoring the full area of facial skin microcirculation would help to identify the condition of Bell's palsy patients. In this study, a non-invasive, real time and full field imaging technology - laser speckle imaging (LSI) technology was applied for measuring facial skin blood perfusion distribution of Bell's palsy patients. 85 participants with different stage of Bell's palsy were included. Results showed that Bell's palsy patients' facial skin perfusion of affected side was lower than that of the normal side at the region of eyelid, and that the asymmetric distribution of the facial skin perfusion between two sides of eyelid is positively related to the stage of the disease (P < 0.001). During the recovery, the perfusion of affected side of eyelid was increasing to nearly the same with the normal side. This study was a novel application of LSI in evaluating the facial skin perfusion of Bell's palsy patients, and we discovered that the facial skin blood perfusion could reflect the stage of Bell's palsy, which suggested that microcirculation should be investigated in patients with this neurological deficit. It was also suggested LSI as potential diagnostic tool for Bell's palsy.
Delles, Michael; Schalck, Sebastian; Chassein, Yves; Müller, Tobias; Rengier, Fabian; Speidel, Stefanie; von Tengg-Kobligk, Hendrik; Kauczor, Hans-Ulrich; Dillmann, Rüdiger; Unterhinninghofen, Roland
Patient-specific blood pressure values in the human aorta are an important parameter in the management of cardiovascular diseases. A direct measurement of these values is only possible by invasive catheterization at a limited number of measurement sites. To overcome these drawbacks, two non-invasive approaches of computing patient-specific relative aortic blood pressure maps throughout the entire aortic vessel volume are investigated by our group. The first approach uses computations from complete time-resolved, three-dimensional flow velocity fields acquired by phasecontrast magnetic resonance imaging (PC-MRI), whereas the second approach relies on computational fluid dynamics (CFD) simulations with ultrasound-based boundary conditions. A detailed evaluation of these computational methods under realistic conditions is necessary in order to investigate their overall robustness and accuracy as well as their sensitivity to certain algorithmic parameters. We present a comparative study of the two blood pressure computation methods in an experimental phantom setup, which mimics a simplified thoracic aorta. The comparative analysis includes the investigation of the impact of algorithmic parameters on the MRI-based blood pressure computation and the impact of extracting pressure maps in a voxel grid from the CFD simulations. Overall, a very good agreement between the results of the two computational approaches can be observed despite the fact that both methods used completely separate measurements as input data. Therefore, the comparative study of the presented work indicates that both non-invasive pressure computation methods show an excellent robustness and accuracy and can therefore be used for research purposes in the management of cardiovascular diseases.
Vähäkuopus, S; Vuento, R; Siljander, T; Syrjänen, J; Vuopio, J
Our study describes the emm type distributions of invasive and non-invasive group A streptococci (GAS) and group G streptococci (GGS) strains in one of the biggest Health Districts in Finland. A total of 571 GAS or GGS were recovered from patients with invasive or non-invasive infections during a 1-year period in 2008-2009 in Pirkanmaa Health District in Finland. We describe here the emm type distributions of GAS and GGS collected from throat (n = 246), pus (n = 217), deep tissue (n = 56) and blood (n = 52). The most common emm types among GAS were emm77, emm1, emm28, emm89 and emm12. Among GGS, the most common emm types were stG480, stG643, stG6, stC6979 and stG485. Some emm types were found to associate with certain infection focus. In GAS, emm77 associated with pus isolates, whereas emm1 and emm12 were more frequent among throat isolates. In GGS, stG480 was more commonly found from throat isolates.
Laqua, Daniel; Pollnow, Stefan; Fischer, Jan; Ley, Sebastian; Husar, Peter
Arterial oxygen saturation of the fetus is an important parameter for monitoring its physical condition. During labor and delivery the transabdominal non-invasive fetal pulse oximetry could minimize the risk for mother and fetus, compared to other existing invasive examination methods. In this contribution, we developed a physical-like phantom to investigate new sensor circuits and algorithms of a non-invasive diagnostic method for fetal pulse oximetry. Hence, the developed artificial vascular system consists of two independent tube systems representing the maternal and fetal vessel system. The arterial blood pressure is reproduced with a pre-pressure and an artificial vascular system. Each pulse wave can be reproduced, by digital control of a proportional valve, adjustable viscoelastic elements, and resistances. The measurements are performed by pressure transducers, optical sensor units, and a coplanar capacitive sensor. Transmission and reflection measurements have shown that the fetal and maternal pulse waves can be reproduced qualitatively. The measured light represents the transabdominal modulated signal on an abdomen of a pregnant woman.
Kawai, Hiroshi; Kudo, Naomi; Kawashima, Yoichi; Mitsumoto, Atsushi
Estimation of liver damage is important in the pathophysiological and toxicological study of liver disease. As a novel, non-invasive marker of liver damage, we studied the efficacy of urine bile acids (UBA) in a rat model of liver disease. Thioacetamide (TAA)-treated rats were used in this study. Single intraperitoneal administration of high-dose TAA induces severe damage to the liver, and thus is used as a model of acute hepatitis. Continuous administration of low-dose TAA yields mild damage to the liver, and induces cirrhosis and hepatic tumors. In this study, it was found that both acute and chronic administration of TAA was associated with a dose-dependent elevation of UBA. The elevation of UBA content correlated with the alteration of blood biochemical indicators, and UBA screening showed a remarkable ability to distinguish liver-damaged rats from healthy rats. In particular, UBA analysis was found to have high sensitivity, specificity, and positive predictive value for the screening of rats with abnormal serum alkaline phosphatase (ALP) activity due to chronic liver damage, which was confirmed to include cholestasis and subsequent cirrhosis by liver histological analysis. In conclusion, we demonstrated that measurement of UBA is a simple, non-invasive and effective method for the screening of cholestasis in TAA-treated rats. We suggest that UBA analysis may have potent applicability for monitoring the progress of liver damage in animal models of chronic liver disease, such as cirrhosis and hepatic encephalopathy.
Pancreatic cancer (PC) is probably the most lethal tumor being forecast as the second most fatal cancer by 2020 in developed countries. Only the earliest forms of the disease are a curable disease but it has to be diagnosed before symptoms starts. Detection at curable phase demands screening intervention for early detection and differential diagnosis. Unfortunately, no successful strategy or image technique has been concluded as effective approach and currently non-invasive biomarkers are the hope. Multiple translational research studies have explored minimally or non-invasive biomarkers in biofluids-blood, urine, stool, saliva or pancreatic juice, but diagnostic performance has not been validated yet. Nowadays no biomarker, alone or in combination, has been superior to carbohydrate antigen 19-9 (CA19-9) in sensitivity and specificity. Although the number of novel biomarkers for early diagnosis of PC has been increasing during the last couple of years, no molecular signature is ready to be implemented in clinical routine. Under the uncertain future, miRNAs profiling and methylation status seem to be the most promising biomarkers. However, good results in larger validations are urgently needed before application. Industry efforts through biotech and pharmaceutical companies are urgently required to demonstrate accuracy and validate promising results from basic and translational results. PMID:27162784
Deng, Han-Yu; Li, Zhi-Hui; Wang, Zhi-Qiang; Wang, Yun-Cang; Li, Gang; Liu, Lun-Xu
Background A challenge for resection of thoracic inlet tumors lies in that high risk of injuring vital blood vessels and brachial plexus still exists during the resection. And the standard surgical approach for resection of thoracic inlet tumors has not yet been well established. Methods Small cervical incision-assisted minimally invasive surgical technique was developed and carried out in patients with non-invasive thoracic inlet tumor in our department. Results We successfully performed the small cervical incision-assisted minimally invasive surgery in two patients with thoracic inlet tumors. The thoracic inlet tumors of the two patients were removed completely without any postoperative complications, and the patients achieved quick rehabilitation after surgery. This combined approach compensates the blind area of thoracoscope in visualizing the superior end of thoracic inlet tumors, and thus enables us to complete the resection safely and confidently. Conclusions Small cervical incision did facilitate the minimally invasive resection of non-invasive thoracic inlet tumor. Hopefully, this combined approach of video-assisted thoracoscopic surgery (VATS) with small cervical incision could be widely utilized in resecting thoracic inlet tumors by general thoracic surgeon. PMID:27867570
Shimizu, M. (Inventor)
A non-invasive method and apparatus is disclosed for measuring pressure within a pliable vessel such as a blood vessel. The blood vessel is clamped by means of a clamping structure having a first portion housing a pressure sensor and a second portion extending over the remote side of the blood vessel for pressing the blood vessel into engagement with the pressure sensing device. The pressure sensing device includes a flat deflectable diaphragm portion arranged to engage a portion of the blood vessel flattened against the diaphragm by means of the clamp structure. In one embodiment, the clamp structure includes first and second semicylindrical members held together by retaining rings. In a second embodiment the clamp structure is of one piece construction having a solid semicylindrical portion and a hollow semicylindrical portion with a longitudinal slot in the follow semicylindrical portion through which a slip the blood vessel. In a third embodiment, an elastic strap is employed for clamping the blood vessel against the pressure sensing device.
Bolognesi, Massimo; Di Pascoli, Marco; Sacerdoti, David
Measurement of portal pressure is pivotal in the evaluation of patients with liver cirrhosis. The measurement of the hepatic venous pressure gradient represents the reference method by which portal pressure is estimated. However, it is an invasive procedure that requires significant hospital resources, including experienced staff, and is associated with considerable cost. Non-invasive methods that can be reliably used to estimate the presence and the degree of portal hypertension are urgently needed in clinical practice. Biochemical and morphological parameters have been proposed for this purpose, but have shown disappointing results overall. Splanchnic Doppler ultrasonography and the analysis of microbubble contrast agent kinetics with contrast-enhanced ultrasonography have shown better accuracy for the evaluation of patients with portal hypertension. A key advancement in the non-invasive evaluation of portal hypertension has been the introduction in clinical practice of methods able to measure stiffness in the liver, as well as stiffness/congestion in the spleen. According to the data published to date, it appears to be possible to rule out clinically significant portal hypertension in patients with cirrhosis (i.e., hepatic venous pressure gradient ≥ 10 mmHg) with a level of clinically-acceptable accuracy by combining measurements of liver stiffness and spleen stiffness along with Doppler ultrasound evaluation. It is probable that the combination of these methods may also allow for the identification of patients with the most serious degree of portal hypertension, and ongoing research is helping to ensure progress in this field.
Jiang, Jingying; Gong, Qiliang; Zou, Da; Xu, Kexin
Since the abnormal metabolism of bilirubin could lead to diseases in the human body, especially the jaundice which is harmful to neonates. Traditional invasive measurements are difficult to be accepted by people because of pain and infection. Therefore, the real-time and non-invasive measurement of bilirubin is of great significance. However, the accuracy of currently transcutaneous bilirubinometry(TcB) is generally not high enough, and affected by many factors in the human skin, mostly by hemoglobin. In this talk, absorption spectra of hemoglobin and bilirubin have been collected and analyzed, then the Partial Least Squares (PLS) models have been built. By analyzing and comparing the Correlation and Root Mean Square Error of Prediction(RMSEP), the results show that the Correlation of bilirubin solution model is larger than that of the mixture solution added with hemoglobin, and its RMSEP value is smaller than that of mixture solution. Therefore, hemoglobin has influences on the non-invasive optical bilirubin sensing. In next step, it is necessary to investigate how to eliminate the influence.
Fecteau, Shirley; Boggio, Paulo; Fregni, Felipe; Pascual-Leone, Alvaro
Deceptive abilities have long been studied in relation to personality traits. More recently, studies explored the neural substrates associated with deceptive skills suggesting a critical role of the prefrontal cortex. Here we investigated whether non-invasive brain stimulation over the dorsolateral prefrontal cortex (DLPFC) could modulate generation of untruthful responses about subject’s personal life across contexts (i.e., deceiving on guilt-free questions on daily activities; generating previously memorized lies about past experience; and producing spontaneous lies about past experience), as well as across modality responses (verbal and motor responses). Results reveal that real, but not sham, transcranial direct current stimulation (tDCS) over the DLPFC can reduce response latency for untruthful over truthful answers across contexts and modality responses. Also, contexts of lies seem to incur a different hemispheric laterality. These findings add up to previous studies demonstrating that it is possible to modulate some processes involved in generation of untruthful answers by applying non-invasive brain stimulation over the DLPFC and extend these findings by showing a differential hemispheric contribution of DLPFCs according to contexts. PMID:23550273
Drucker, Caroline B.; Carlson, Monica L.; Toda, Koji; DeWind, Nicholas K.; Platt, Michael L.
Background The success of many neuroscientific studies depends upon adequate head fixation of awake, behaving animals. Typically, this is achieved by surgically affixing a head-restraint prosthesis to the skull. New Method Here we report the use of thermoplastic masks to non-invasively restrain monkeys’ heads. Mesh thermoplastic sheets become pliable when heated and can then be molded to an individual monkey’s head. After cooling, the custom mask retains this shape indefinitely for day-to-day use. Results We successfully trained rhesus macaques (Macaca mulatta) to perform cognitive tasks while wearing thermoplastic masks. Using these masks, we achieved a level of head stability sufficient for high-resolution eye-tracking and intracranial electrophysiology. Comparison with Existing Method Compared with traditional head-posts, we find that thermoplastic masks perform at least as well during infrared eye-tracking and single-neuron recordings, allow for clearer magnetic resonance image acquisition, enable freer placement of a transcranial magnetic stimulation coil, and impose lower financial and time costs on the lab. Conclusions We conclude that thermoplastic masks are a viable non-invasive form of primate head restraint that enable a wide range of neuroscientific experiments. PMID:26112334
Bolognesi, Massimo; Di Pascoli, Marco; Sacerdoti, David
Measurement of portal pressure is pivotal in the evaluation of patients with liver cirrhosis. The measurement of the hepatic venous pressure gradient represents the reference method by which portal pressure is estimated. However, it is an invasive procedure that requires significant hospital resources, including experienced staff, and is associated with considerable cost. Non-invasive methods that can be reliably used to estimate the presence and the degree of portal hypertension are urgently needed in clinical practice. Biochemical and morphological parameters have been proposed for this purpose, but have shown disappointing results overall. Splanchnic Doppler ultrasonography and the analysis of microbubble contrast agent kinetics with contrast-enhanced ultrasonography have shown better accuracy for the evaluation of patients with portal hypertension. A key advancement in the non-invasive evaluation of portal hypertension has been the introduction in clinical practice of methods able to measure stiffness in the liver, as well as stiffness/congestion in the spleen. According to the data published to date, it appears to be possible to rule out clinically significant portal hypertension in patients with cirrhosis (i.e., hepatic venous pressure gradient ≥ 10 mmHg) with a level of clinically-acceptable accuracy by combining measurements of liver stiffness and spleen stiffness along with Doppler ultrasound evaluation. It is probable that the combination of these methods may also allow for the identification of patients with the most serious degree of portal hypertension, and ongoing research is helping to ensure progress in this field. PMID:28104976
Stasi, Cristina; Milani, Stefano
Transient elastography and the acoustic radiation force impulse techniques may play a pivotal role in the study of liver fibrosis. Some studies have shown that elastography can detect both the progression and regression of fibrosis. Similarly, research results have been analysed and direct and indirect serum markers of hepatic fibrosis have shown high diagnostic accuracy for advanced fibrosis/cirrhosis. The prognosis of different stages of cirrhosis is well established and various staging systems have been proposed, largely based on clinical data. However, it is still unknown if either non-invasive markers of liver fibrosis or elastography may contribute to a more accurate staging of liver cirrhosis, in terms of prognosis and fibrosis regression after effective therapy. In fact, not enough studies have shown both the fibrosis regression in different cirrhosis stages and the point beyond which the prognosis does not change - even in the event of fibrosis regression. Therefore, future studies are needed to validate non-invasive methods in predicting the different phases of liver cirrhosis. PMID:28127192
Lurie, Yoav; Webb, Muriel; Cytter-Kuint, Ruth; Shteingart, Shimon; Lederkremer, Gerardo Z
The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect; even according to its proponents, it is only "the best" among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future.
Mainenti, Pier Paolo; Romano, Federica; Pizzuti, Laura; Segreto, Sabrina; Storto, Giovanni; Mannelli, Lorenzo; Imbriaco, Massimo; Camera, Luigi; Maurea, Simone
Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases (CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liver-directed therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs. PMID:26217455
Mainenti, Pier Paolo; Romano, Federica; Pizzuti, Laura; Segreto, Sabrina; Storto, Giovanni; Mannelli, Lorenzo; Imbriaco, Massimo; Camera, Luigi; Maurea, Simone
Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases (CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liver-directed therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs.
Chi, Richard P; Fregni, Felipe; Snyder, Allan W
Our visual memories are susceptible to errors, but less so in people who have a more literal cognitive style. This inspired us to attempt to improve visual memory with non-invasive brain stimulation. We applied 13 min of bilateral transcranial direct current stimulation (tDCS) to the anterior temporal lobes. Our stimulation protocol included 3 conditions, each with 12 neurotypical participants: (i) left cathodal stimulation together with right anodal stimulation, (ii) left anodal stimulation together with right cathodal stimulation, and (iii) sham (control) stimulation. Only participants who received left cathodal stimulation (decrease in excitability) together with right anodal stimulation (increase in excitability) showed an improvement in visual memory. This 110% improvement in visual memory was similar to the advantage people with autism, who are known to be more literal, show over normal people in the identical visual task. Importantly, participants receiving stimulation of the opposite polarity (left anodal together with right cathodal stimulation) failed to show any change in memory performance. This is the first demonstration that visual memory can be enhanced in healthy people using non-invasive brain stimulation.
Jerem, Paul; Herborn, Katherine; McCafferty, Dominic; McKeegan, Dorothy; Nager, Ruedi
Stress, a central concept in biology, describes a suite of emergency responses to challenges. Among other responses, stress leads to a change in blood flow that results in a net influx of blood to key organs and an increase in core temperature. This stress-induced hyperthermia is used to assess stress. However, measuring core temperature is invasive. As blood flow is redirected to the core, the periphery of the body can cool. This paper describes a protocol where peripheral body temperature is measured non-invasively in wild blue tits (Cyanistes caeruleus) using infrared thermography. In the field we created a set-up bringing the birds to an ideal position in front of the camera by using a baited box. The camera takes a short thermal video recording of the undisturbed bird before applying a mild stressor (closing the box and therefore capturing the bird), and the bird’s response to being trapped is recorded. The bare skin of the eye-region is the warmest area in the image. This allows an automated extraction of the maximum eye-region temperature from each image frame, followed by further steps of manual data filtering removing the most common sources of errors (motion blur, blinking). This protocol provides a time series of eye-region temperature with a fine temporal resolution that allows us to study the dynamics of the stress response non-invasively. Further work needs to demonstrate the usefulness of the method to assess stress, for instance to investigate whether eye-region temperature response is proportional to the strength of the stressor. If this can be confirmed, it will provide a valuable alternative method of stress assessment in animals and will be useful to a wide range of researchers from ecologists, conservation biologists, physiologists to animal welfare researchers. PMID:26575985
Denoising is critical to improving the quality and stability of cerebral blood flow (CBF) quantification in arterial spin labeled (ASL) perfusion magnetic resonance imaging (MRI) due to the intrinsic low signal-to-noise-ratio (SNR) of ASL data. Previous studies have been focused on reducing the spatial or temporal noise using standard filtering techniques, and less attention has been paid to two global nuisance effects, the residual motion artifacts and the global signal fluctuations. Since both nuisances affect the whole brain, removing them in advance should enhance the CBF quantification quality for ASL MRI. The purpose of this paper was to assess this potential benefit. Three methods were proposed to suppress each or both of the two global nuisances. Their performances for CBF quantification were validated using ASL data acquired from 13 subjects. Evaluation results showed that covarying out both global nuisances significantly improved temporal SNR and test-retest stability of CBF measurement. Although the concept of removing both nuisances is not technically novel per se, this paper clearly showed the benefits for ASL CBF quantification. Dissemination of the proposed methods in a free ASL data processing toolbox should be of interest to a broad range of ASL users.
Stewart, Stephanie B; Koller, Jonathan M; Campbell, Meghan C; Perlmutter, Joel S; Black, Kevin J
To determine how different methods of normalizing for global cerebral blood flow (gCBF) affect image quality and sensitivity to cortical activation, pulsed arterial spin labeling (pASL) scans obtained during a visual task were normalized by either additive or multiplicative normalization of modal gCBF. Normalization by either method increased the statistical significance of cortical activation by a visual stimulus. However, image quality was superior with additive normalization, whether judged by intensity histograms or by reduced variability within gray and white matter.
Wang, Xiaoxiao; Chen, Song; Chen, Gang
ABH antigens are not expressed on the red blood cells of monkeys, making it difficult to accurately determine their blood type. In this study, we evaluated the feasibility, convenience, and stability of two non-invasive methods for ABO typing (a reverse gel system assay and a buccal mucosal cell immunofluorescent assay) in cynomolgus monkeys (n = 72). The renal tissue immunofluorescent assay was used to obtain an accurate blood type in the monkeys. Using the reverse gel system assay and preabsorbed serum, we achieved accurate detection of ABO blood groups in 65 of the 72 monkeys but obtained confusing results in the remaining 7. The original immunofluorescent staining of the buccal mucosal smears clearly and correctly identified the ABO blood groups in 50 of the 72 monkeys. After repeated smearing and staining, the ABO group type could be correctly identified in samples from the rest of the monkeys, which were either lacking sufficient buccal mucosal cells or contained impurities. Based on our findings, we recommend the reverse gel system assay as the first choice for primate blood type analysis, and the buccal mucosal cell immunofluorescent assay as a Supplementary Method whenever the reverse gel system assay fails to give a clear result. PMID:28112245
König, Karsten; Riemann, Iris; Ehlers, Alexander; Le Harzic, Ronan
High resolution non-invasive 3D imaging devices are required to detect pathogenic microorganisms such as Anthrax spores, bacteria, viruses, fungi and chemical agents entering biological tissues such as the epidermis. Due to the low light penetration depth and the biodamage potential, ultraviolet light sources can not be employed to realize intratissue imaging of bio- and chemohazards. We report on the novel near infrared laser technology multiphoton tomography and the high resolution 4D imaging tool DermaInspect for non-invasive detection of intratissue agents and their influence on cellular metabolism based on multiphoton autofluorescence imaging (MAI) and second harmonic generation (SHG). Femtosecond laser pulses in the spectral range of 750 nm to 850 nm have been used to image in vivo human skin with subcellular spatial and picosecond temporal resolution. The non-linear induced autofluorescence of both, skin tissues and microorganisms, originates mainly from naturally endogenous fluorophores/protein structures like NAD(P)H, flavins, keratin, collagen, elastin, porphyrins and melanin. Bacteria emit in the blue/green spectral range due to NAD(P)H and flavoproteins and, in certain cases, in the red spectral range due to the biosynthesis of Zn-porphyrins, coproporphyrin and protoporphyrin. Collagen and exogenous non-centrosymmetric molecules can be detected by SHG signals. The system DermaInspect consists of a wavelength-tunable compact 80/90 MHz Ti:sapphire laser, a scan module with galvo scan mirrors, piezo-driven objective, fast photon detector and time-resolved single photon counting unit. It can be used to perform optical sectioning and 3D autofluorescence lifetime imaging (τ-mapping) with 1 μm spatial resolution and 270 ps temporal resolution. The parameter fluorescence lifetime depends on the type of fluorophore and its microenvironment and can be used to distinguish bio- and chemohazards from cellular background and to gain information for pathogen
Grimaldi, G; Argyropoulos, G P; Boehringer, A; Celnik, P; Edwards, M J; Ferrucci, R; Galea, J M; Groiss, S J; Hiraoka, K; Kassavetis, P; Lesage, E; Manto, M; Miall, R C; Priori, A; Sadnicka, A; Ugawa, Y; Ziemann, U
The field of neurostimulation of the cerebellum either with transcranial magnetic stimulation (TMS; single pulse or repetitive (rTMS)) or transcranial direct current stimulation (tDCS; anodal or cathodal) is gaining popularity in the scientific community, in particular because these stimulation techniques are non-invasive and provide novel information on cerebellar functions. There is a consensus amongst the panel of experts that both TMS and tDCS can effectively influence cerebellar functions, not only in the motor domain, with effects on visually guided tracking tasks, motor surround inhibition, motor adaptation and learning, but also for the cognitive and affective operations handled by the cerebro-cerebellar circuits. Verbal working memory, semantic associations and predictive language processing are amongst these operations. Both TMS and tDCS modulate the connectivity between the cerebellum and the primary motor cortex, tuning cerebellar excitability. Cerebellar TMS is an effective and valuable method to evaluate the cerebello-thalamo-cortical loop functions and for the study of the pathophysiology of ataxia. In most circumstances, DCS induces a polarity-dependent site-specific modulation of cerebellar activity. Paired associative stimulation of the cerebello-dentato-thalamo-M1 pathway can induce bidirectional long-term spike-timing-dependent plasticity-like changes of corticospinal excitability. However, the panel of experts considers that several important issues still remain unresolved and require further research. In particular, the role of TMS in promoting cerebellar plasticity is not established. Moreover, the exact positioning of electrode stimulation and the duration of the after effects of tDCS remain unclear. Future studies are required to better define how DCS over particular regions of the cerebellum affects individual cerebellar symptoms, given the topographical organization of cerebellar symptoms. The long-term neural consequences of non-invasive
Antonacci, Giuseppe; Braakman, Sietse
Cellular biomechanics play a pivotal role in the pathophysiology of several diseases. Unfortunately, current methods to measure biomechanical properties are invasive and mostly limited to the surface of a cell. As a result, the mechanical behaviour of subcellular structures and organelles remains poorly characterised. Here, we show three-dimensional biomechanical images of single cells obtained with non-invasive, non-destructive Brillouin microscopy with an unprecedented spatial resolution. Our results quantify the longitudinal elastic modulus of subcellular structures. In particular, we found the nucleoli to be stiffer than both the nuclear envelope (p < 0.0001) and the surrounding cytoplasm (p < 0.0001). Moreover, we demonstrate the mechanical response of cells to Latrunculin-A, a drug that reduces cell stiffness by preventing cytoskeletal assembly. Our technique can therefore generate valuable insights into cellular biomechanics and its role in pathophysiology. PMID:27845411
Litteken, Douglas A.; Daum, Jared S.
The need for lightweight and non-intrusive tension measurements has arisen alongside the development of high-fidelity computer models of textile and fluid dynamics. In order to validate these computer models, data must be gathered in the operational environment without altering the design, construction, or performance of the test article. Current measurement device designs rely on severing a cord and breaking the load path to introduce a load cell. These load cells are very reliable, but introduce an area of high stiffness in the load path, directly affecting the structural response, adding excessive weight, and possibly altering the dynamics of the parachute during a test. To capture the required data for analysis validation without affecting the response of the system, non-invasive measurement devices have been developed and tested by NASA. These tension measurement devices offer minimal impact to the mass, form, fit, and function of the test article, while providing reliable, axial tension measurements for parachute cordage.
Agarwal, R; Aggarwal, A; Gupta, D; Jindal, S
Non-invasive ventilation (NIV) is the delivery of assisted mechanical ventilation to the lungs, without the use of an invasive endotracheal airway. NIV has revolutionised the management of patients with various forms of respiratory failure. It has decreased the need for invasive mechanical ventilation and its attendant complications. Cardiogenic pulmonary oedema (CPO) is a common medical emergency, and NIV has been shown to improve both physiological and clinical outcomes. From the data presented herein, it is clear that there is sufficiently high level evidence to favour the use of continuous positive airway pressure (CPAP), and that the use of CPAP in patients with CPO decreases intubation rate and improves survival (number needed to treat seven and eight respectively). However, there is insufficient evidence to recommend the use of bilevel positive airway pressure (BiPAP), probably the exception being patients with hypercapnic CPO. More trials are required to conclusively define the role of BiPAP in CPO. PMID:16210459
Darby, R. Ryan; Pascual-Leone, Alvaro
Biomedical enhancement refers to the use of biomedical interventions to improve capacities beyond normal, rather than to treat deficiencies due to diseases. Enhancement can target physical or cognitive capacities, but also complex human behaviors such as morality. However, the complexity of normal moral behavior makes it unlikely that morality is a single capacity that can be deficient or enhanced. Instead, our central hypothesis will be that moral behavior results from multiple, interacting cognitive-affective networks in the brain. First, we will test this hypothesis by reviewing evidence for modulation of moral behavior using non-invasive brain stimulation. Next, we will discuss how this evidence affects ethical issues related to the use of moral enhancement. We end with the conclusion that while brain stimulation has the potential to alter moral behavior, such alteration is unlikely to improve moral behavior in all situations, and may even lead to less morally desirable behavior in some instances. PMID:28275345
LaBlance, G R; Steckol, K F; Cooper, M H
Evaluation of vocal pathology and the accompanying dysphonia should include an assessment of laryngeal structure and mobility as well as respiratory dynamics. Laryngeal structure is best observed through laryngoscopy which provides an accurate assessment of the tissues and their mobility. Respiratory measures of lung volume, air-flow and pressure, and breathing dynamics are typically determined via spirometry and pneumotachography. While the above are traditional invasive procedures which interfere with normal speech production, recent advances in electronic technology have resulted in the development of non-invasive procedures to assess phonatory and respiratory dynamics. These procedures, when used as an adjunct to laryngoscopy, can provide information that is useful in the diagnosis and management of vocal tract dysfunction. The Laryngograph and Computer-Aided Fluency Establishment Trainer, described here, are examples of this new technology.
Gajo, Gianandrea; Pollak, Pierre; Lüscher, Christian; Benninger, David
Parkinson's disease (PD) is a major socio-economic burden increasing with the aging population. In advanced PD, the emergence of symptoms refractory to conventional therapy poses a therapeutic challenge. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in non-invasive brain stimulation (NIBS) as an alternative therapeutic tool. NIBS could offer an alternative approach for patients at risk who are excluded from surgery and/or to treat refractory symptoms. The treatment of the freezing of gait, a major cause of disability and falls in PD patients, could be enhanced by transcranial direct current stimulation (tDCS). A therapeutic study is currently performed at the Department of Neurology at the CHUV.
Toews, Maeghan; Caulfield, Timothy
Although non-invasive prenatal testing (NIPT) marks a notable development in the field of prenatal genetic testing, there are some physician liability considerations raised by this technology. As NIPT is still emerging as the standard of care and is just starting to receive provincial funding, the question arises of whether physicians are obligated to disclose the availability of NIPT to eligible patients as part of the physician-patient discussion about prenatal screening and diagnosis. If NIPT is discussed with patients, it is important to disclose the limitations of this technology with respect to its accuracy and the number of disorders that it can detect when compared with invasive diagnostic options. A failure to sufficiently disclose these limitations could leave patients with false assurances about the health of their fetuses and could raise informed consent and liability issues, particularly if a child is born with a disability as a result.
Strangman, Gary; Boas, David A.; Sutton, Jeffrey P.
This article reviews diffuse optical brain imaging, a technique that employs near-infrared light to non-invasively probe the brain for changes in parameters relating to brain function. We describe the general methodology, including types of measurements and instrumentation (including the tradeoffs inherent in the various instrument components), and the basic theory required to interpret the recorded data. A brief review of diffuse optical applications is included, with an emphasis on research that has been done with psychiatric populations. Finally, we discuss some practical issues and limitations that are relevant when conducting diffuse optical experiments. We find that, while diffuse optics can provide substantial advantages to the psychiatric researcher relative to the alternative brain imaging methods, the method remains substantially underutilized in this field.
Müri, René Martin; Cazzoli, Dario; Nef, Tobias; Mosimann, Urs P.; Hopfner, Simone; Nyffeler, Thomas
Here, we review the effects of non-invasive brain stimulation such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) in the rehabilitation of neglect. We found 12 studies including 172 patients (10 TMS studies and 2 tDCS studies) fulfilling our search criteria. Activity of daily living measures such as the Barthel Index or, more specifically for neglect, the Catherine Bergego Scale were the outcome measure in three studies. Five studies were randomized controlled trials with a follow-up time after intervention of up to 6 weeks. One TMS study fulfilled criteria for Class I and one for Class III evidence. The studies are heterogeneous concerning their methodology, outcome measures, and stimulation parameters making firm comparisons and conclusions difficult. Overall, there are however promising results for theta-burst stimulation, suggesting that TMS is a powerful add-on therapy in the rehabilitation of neglect patients. PMID:23772209
Welch, Jeanne A.
The invention relates generally to measuring devices and to devices for measuring the pressure in a sealed container. More particularly, the invention relates to a non-invasive device and method for measuring the pressure of a gas in a double-envelope lamp. An infrared gaseous discharge lamp of integrated double-envelope construction has an inner chamber or envelope filled with a gaseous medium under relatively high pressure which provides illumination when the lamp is energized. The outer chamber or envelope is normally evacuated or otherwise provided with a relatively low-pressure gas. Double-envelope lamps are subject to gas leaks from the inner chamber to the outer chamber. Eventually, these leaks may lead to catastrophic lamp failure by a mechanism that involves electric arcing in the outer chamber.
Soldovieri, Francesco; Masini, Nicola
The relevance of the information produced by science and technology for the knowledge of the cultural heritage depends on the quality of the feedback and, consequently, on the "cultural" distance between scientists and end-users. In particular, the solution to this problem mainly resides in the capability of end-users' capability to assess and transform the knowledge produced by diagnostics with regard to: information on both cultural objects and sites (decay patterns, vulnerability, presence of buried archaeological remains); decision making (management plan, conservation project, and excavation plan). From our experience in the field of the cultural heritage and namely the conservation, of monuments, there is a significant gap of information between technologists (geophysicists/physicists/engineers) and end-users (conservators/historians/architects). This cultural gap is due to the difficulty to interpret "indirect data" produced by non invasive diagnostics (i.e. radargrams/thermal images/seismic tomography etc..) in order to provide information useful to improve the historical knowledge (e.g. the chronology of the different phases of a building), to characterise the state of conservation (e.g. detection of cracks in the masonry) and to monitor in time cultural heritage artifacts and sites. The possible answer to this difficulty is in the set-up of a knowledge chain regarding the following steps: - Integrated application of novel and robust data processing methods; - Augmented reality as a tool for making easier the interpretation of non invasive - investigations for the analysis of decay pathologies of masonry and architectural surfaces; - The comparison between direct data (carrots, visual inspection) and results from non-invasive tests, including geophysics, aims to improve the interpretation and the rendering of the monuments and even of the archaeological landscapes; - The use of specimens or test beds for the detection of archaeological features and
Darby, R Ryan; Pascual-Leone, Alvaro
Biomedical enhancement refers to the use of biomedical interventions to improve capacities beyond normal, rather than to treat deficiencies due to diseases. Enhancement can target physical or cognitive capacities, but also complex human behaviors such as morality. However, the complexity of normal moral behavior makes it unlikely that morality is a single capacity that can be deficient or enhanced. Instead, our central hypothesis will be that moral behavior results from multiple, interacting cognitive-affective networks in the brain. First, we will test this hypothesis by reviewing evidence for modulation of moral behavior using non-invasive brain stimulation. Next, we will discuss how this evidence affects ethical issues related to the use of moral enhancement. We end with the conclusion that while brain stimulation has the potential to alter moral behavior, such alteration is unlikely to improve moral behavior in all situations, and may even lead to less morally desirable behavior in some instances.
Antonacci, Giuseppe; Braakman, Sietse
Cellular biomechanics play a pivotal role in the pathophysiology of several diseases. Unfortunately, current methods to measure biomechanical properties are invasive and mostly limited to the surface of a cell. As a result, the mechanical behaviour of subcellular structures and organelles remains poorly characterised. Here, we show three-dimensional biomechanical images of single cells obtained with non-invasive, non-destructive Brillouin microscopy with an unprecedented spatial resolution. Our results quantify the longitudinal elastic modulus of subcellular structures. In particular, we found the nucleoli to be stiffer than both the nuclear envelope (p < 0.0001) and the surrounding cytoplasm (p < 0.0001). Moreover, we demonstrate the mechanical response of cells to Latrunculin-A, a drug that reduces cell stiffness by preventing cytoskeletal assembly. Our technique can therefore generate valuable insights into cellular biomechanics and its role in pathophysiology.
Min, James K; Hasegawa, James T; Machacz, Susanne F; O'Day, Ken
This study compared costs and clinical outcomes of invasive versus non-invasive diagnostic evaluations for patients with suspected in-stent restenosis (ISR) after percutaneous coronary intervention. We developed a decision model to compare 2 year diagnosis-related costs for patients who presented with suspected ISR and were evaluated by: (1) invasive coronary angiography (ICA); (2) non-invasive stress testing strategy of myocardial perfusion imaging (MPI) with referral to ICA based on MPI; (3) coronary CT angiography-based testing strategy with referral to ICA based on CCTA. Costs were modeled from the payer's perspective using 2014 Medicare rates. 56 % of patients underwent follow-up diagnostic testing over 2 years. Compared to ICA, MPI (98.6 %) and CCTA (98.1 %) exhibited lower rates of correct diagnoses. Non-invasive strategies were associated with reduced referrals to ICA and costs compared to an ICA-based strategy, with diagnostic costs lower for CCTA than MPI. Overall 2-year costs were highest for ICA for both metallic as well as BVS stents ($1656 and $1656, respectively) when compared to MPI ($1444 and $1411) and CCTA. CCTA costs differed based upon stent size and type, and were highest for metallic stents >3.0 mm followed by metallic stents <3.0 mm, BVS < 3.0 mm and BVS > 3.0 mm ($1466 vs. $1242 vs. $855 vs. $490, respectively). MPI for suspected ISR results in lower costs and rates of complications than invasive strategies using ICA while maintaining high diagnostic performance. Depending upon stent size and type, CCTA results in lower costs than MPI.
Hasegawa, James T.; Machacz, Susanne F.; O’Day, Ken
This study compared costs and clinical outcomes of invasive versus non-invasive diagnostic evaluations for patients with suspected in-stent restenosis (ISR) after percutaneous coronary intervention. We developed a decision model to compare 2 year diagnosis-related costs for patients who presented with suspected ISR and were evaluated by: (1) invasive coronary angiography (ICA); (2) non-invasive stress testing strategy of myocardial perfusion imaging (MPI) with referral to ICA based on MPI; (3) coronary CT angiography-based testing strategy with referral to ICA based on CCTA. Costs were modeled from the payer’s perspective using 2014 Medicare rates. 56 % of patients underwent follow-up diagnostic testing over 2 years. Compared to ICA, MPI (98.6 %) and CCTA (98.1 %) exhibited lower rates of correct diagnoses. Non-invasive strategies were associated with reduced referrals to ICA and costs compared to an ICA-based strategy, with diagnostic costs lower for CCTA than MPI. Overall 2-year costs were highest for ICA for both metallic as well as BVS stents ($1656 and $1656, respectively) when compared to MPI ($1444 and $1411) and CCTA. CCTA costs differed based upon stent size and type, and were highest for metallic stents >3.0 mm followed by metallic stents <3.0 mm, BVS < 3.0 mm and BVS > 3.0 mm ($1466 vs. $1242 vs. $855 vs. $490, respectively). MPI for suspected ISR results in lower costs and rates of complications than invasive strategies using ICA while maintaining high diagnostic performance. Depending upon stent size and type, CCTA results in lower costs than MPI. PMID:26335370
Djaberi, R; Beishuizen, E D; Pereira, A M; Rabelink, T J; Smit, J W; Tamsma, J T; Huisman, M V; Jukema, J W
Cardiovascular disease is the major cause of mortality in type 2 diabetes mellitus. The criteria for the selection of those asymptomatic patients with type 2 diabetes who should undergo cardiac screening and the therapeutic consequences of screening remain controversial. Non-invasive techniques as markers of atherosclerosis and myocardial ischaemia may aid risk stratification and the implementation of tailored therapy for the patient with type 2 diabetes. In the present article we review the literature on the implementation of non-invasive vascular tools and cardiac imaging techniques in this patient group. The value of these techniques as endpoints in clinical trials and as risk estimators in asymptomatic diabetic patients is discussed. Carotid intima-media thickness, arterial stiffness and flow-mediated dilation are abnormal long before the onset of type 2 diabetes. These vascular tools are therefore most likely to be useful for the identification of 'at risk' patients during the early stages of atherosclerotic disease. The additional value of these tools in risk stratification and tailored therapy in type 2 diabetes remains to be proven. Cardiac imaging techniques are more justified in individuals with a strong clinical suspicion of advanced coronary heart disease (CHD). Asymptomatic myocardial ischaemia can be detected by stress echocardiography and myocardial perfusion imaging. The more recently developed non-invasive multi-slice computed tomography angiography is recommended for exclusion of CHD, and can therefore be used to screen asymptomatic patients with type 2 diabetes, but has the associated disadvantages of high radiation exposure and costs. Therefore, we propose an algorithm for the screening of asymptomatic diabetic patients, the first step of which consists of coronary artery calcium score assessment and exercise ECG.
Shaharin, Alfi; Krite Svanberg, Emilie; Ellerström, Ida; Subash, Arman Ahamed; Khoptyar, Dmitry; Andersson-Engels, Stefan; Åkeson, Jonas
Muscle tissue saturation (StO2) has been measured with two non-invasive optical techniques and the results were compared. One of the techniques is widely used in the hospitals - the CW-NIRS technique. The other is the photon timeof- flight spectrometer (pTOFS) developed in the Group of Biophotonics, Lund University, Sweden. The wavelengths used in both the techniques are 730 nm and 810 nm. A campaign was arranged to perform measurements on 21 (17 were taken for comparison) healthy adult volunteers (8 women and 13 men). Oxygen saturations were measured at the right lower arm of each volunteer. To observe the effects of different provocations on the oxygen saturation a blood pressure cuff was attached in the upper right arm. For CW-NIRS, the tissue saturation values were in the range from 70-90%, while for pTOFS the values were in the range from 55-60%.
Xiong, Bing; Wei, Wenxiong; Liu, Nan; He, Jian-Jun
Continuous non-invasive glucose monitoring is a powerful tool for the treatment and management of diabetes. A glucose measurement method, with the potential advantage of miniaturizability with no moving parts, based on the frequency modulated continuous wave (FMCW) LIDAR technology is proposed and investigated. The system mainly consists of an integrated near-infrared tunable semiconductor laser and a detector, using heterodyne technology to convert the signal from time-domain to frequency-domain. To investigate the feasibility of the method, Monte Carlo simulations have been performed on tissue phantoms with optical parameters similar to those of human interstitial fluid. The simulation showed that the sensitivity of the FMCW LIDAR system to glucose concentration can reach 0.2mM. Our analysis suggests that the FMCW LIDAR technique has good potential for noninvasive blood glucose monitoring.
Urbanova, Barbora; Tomek, Ales; Mikulik, Robert; Magerova, Hana; Horinek, Daniel; Hort, Jakub
There has been a growing interest in vascular impairment associated with Alzheimer’s disease (AD). This interest was stimulated by the findings of higher incidence of vascular risk factors in AD. Signs of vascular impairment were investigated notably in the field of imaging methods. Our aim was to explore ultrasonographic studies of extra- and intracranial vessels in patients with AD and mild cognitive impairment (MCI) and define implications for diagnosis, treatment, and prevention of the disease. The most frequently studied parameters with extracranial ultrasound are intima-media thickness in common carotid artery, carotid atherosclerosis, and total cerebral blood flow. The transcranial ultrasound concentrates mostly on flow velocities, pulsatility indices, cerebrovascular reserve capacity, and cerebral microembolization. Studies suggest that there is morphological and functional impairment of cerebral circulation in AD compared to healthy subjects. Ultrasound as a non-invasive method could be potentially useful in identifying individuals in a higher risk of progression of cognitive decline. PMID:24478651
Schedler, O; Handschak, H; Hensel, M
In cardiac emergency events (NACA score = 3.4), a non-invasive cardiac output test involving transaortalic blood flow velocity measurement was used in the air rescue of 30 patients. An average velocity integral (Vti) of 21.9 +/- 9.9 cm was determined in the short examination time (t = 120 +/- 30 sec). Related to the middle body surface (BSA = 2.0 +/- 0.3 m (2)), the calculated cardiac index (CI) was 2.6 +/- 1.1 l/min/m (2). The CI was under 2.2 l/min/m (2) in 12 examinations (40 %). 5 patients in this group subsequently received catecholamine therapy. Thrombolysis therapy increased by 17 % in the myocardial infarction group with CI = 2.2 l/min/m (2) by the USCOM measurement. However, the results do not justify a definitive recommendation for application of the USCOM system in air rescue service.
Sumriddetchkajorn, Sarun; Somboonkaew, Armote; Sodsong, Tawee; Promduang, Itthipol; Sumriddetchkajorn, Niti
We have developed a non-invasive thermal image analyzer for deceptive detection (TAD2) where the far-infrared data around the periorbital and nostril areas are simultaneously analyzed. Measured change in maximum skin temperature around two periorbital regions is converted to a relative blood flow velocity. A respiration pattern is also simultaneously determined via the ratio of the measured maximum and minimum temperatures in the nostril area. In addition, our TAD2 employs a simple normalized cross correlation scheme to independently track locations of the two periorbital and nostril areas. Our field case study from 7 subjects in two real crime scenes and with the use of our baseline classification criteria shows two-fold improvement in classification rate compared to our analysis using either the periorbital or nostril area alone.
TRUTA, ANAMARIA; POPON, TUDOR ADRIAN HODOR; SARACI, GEORGE; GHERVAN, LIVIU; POP, IOAN VICTOR
Bladder cancer is one of the most commonly diagnosed malignancies worldwide, derived from the urothelium of the urinary bladder and defined by long asymptomatic and atypical clinical picture. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. Various genetic polymorphisms and microRNA might represent useful diagnostic or prognostic biomarkers. Genetic and molecular abnormalities - risk factors are represented by miRNA or genetic polymorphisms proved to be part of bladder carcinogenesis such as: genetic mutations of oncogenes TP53, Ras, Rb1 or p21 oncoproteins, cyclin D or genetic polymorhisms of XPD,ERCC1, CYP1B1, NQO1C609T, MDM2SNP309, CHEK2, ERCC6, NRF2, NQO1Pro187Ser polymorphism and microRNA (miR-143, −145, −222, −210, −10b, 576-3p). The aim of our article is to highlight the most recent acquisitions via molecular biomarkers (miRNAs and genetic polymorphisms) involved in bladder cancer in order to provide early diagnosis, precise therapy according to the molecular profile of bladder tumors, as well as to improve clinical outcome, survival rates and life quality of oncological patients. These molecular biomarkers play a key role in bladder carcinogenesis, clinical evolution, prognosis and therapeutic response and explain the molecular mechanisms involved in bladder carcinogenesis; they can also be selected as therapeutic targets in developing novel therapeutic strategies in bladder malignancies. Moreover, the purpose in defining these molecular non invasive biomarkers is also to develop non invasive screening programs in bladder malignancies with the result of decreasing bladder cancer incidence in risk population. PMID:27152066
Truta, Anamaria; Popon, Tudor Adrian Hodor; Saraci, George; Ghervan, Liviu; Pop, Ioan Victor
Bladder cancer is one of the most commonly diagnosed malignancies worldwide, derived from the urothelium of the urinary bladder and defined by long asymptomatic and atypical clinical picture. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. Various genetic polymorphisms and microRNA might represent useful diagnostic or prognostic biomarkers. Genetic and molecular abnormalities - risk factors are represented by miRNA or genetic polymorphisms proved to be part of bladder carcinogenesis such as: genetic mutations of oncogenes TP53, Ras, Rb1 or p21 oncoproteins, cyclin D or genetic polymorhisms of XPD,ERCC1, CYP1B1, NQO1C609T, MDM2SNP309, CHEK2, ERCC6, NRF2, NQO1Pro187Ser polymorphism and microRNA (miR-143, -145, -222, -210, -10b, 576-3p). The aim of our article is to highlight the most recent acquisitions via molecular biomarkers (miRNAs and genetic polymorphisms) involved in bladder cancer in order to provide early diagnosis, precise therapy according to the molecular profile of bladder tumors, as well as to improve clinical outcome, survival rates and life quality of oncological patients. These molecular biomarkers play a key role in bladder carcinogenesis, clinical evolution, prognosis and therapeutic response and explain the molecular mechanisms involved in bladder carcinogenesis; they can also be selected as therapeutic targets in developing novel therapeutic strategies in bladder malignancies. Moreover, the purpose in defining these molecular non invasive biomarkers is also to develop non invasive screening programs in bladder malignancies with the result of decreasing bladder cancer incidence in risk population.
Shah, Amy S.; Gao, Zhiqian; Dolan, Lawrence M.; Dabelea, Dana; D'Agostino, Ralph B.; Urbina, Elaine M.
Background Microvascular dysfunction is a key event in the development of atherosclerosis, which predates the clinical manifestations of vascular disease including stroke and myocardial infarction. Dysfunction of the microvasculature can be measured as a decreased microperfusion in response to heat. Objective We sought to evaluate the microvasculature using heat among adolescents and young adults with type 1 diabetes (T1D) compared to healthy non-diabetic controls. We hypothesized that youth with T1D would have impaired microvascular function measured as decreased perfusion. Methods We studied 181 adolescents and young adults with T1D and 96 age-, race-, and sex-matched healthy controls (mean age 19 yr). Patients were seen at an in-person study visit where demographics, anthropometrics, and laboratory data was obtained. Skin microvascular perfusion was measured on the volvar surface of the right forearm using a standard laser flow Doppler. Measurements were taken at baseline and after heating to 44° C. Results Youth with T1D had decreased microvascular perfusion as measured by lower percent change of perfusion units (1870 ± 945 vs. 2539 ± 1255, p < 0.01) and percent change in area under the curve (1870 ± 945 vs. 2539 ± 1255, p < 0.01) compared to controls. Glycosylated hemoglobin A1c (HbA1c) was found to be an independent determinant of microvascular function (p < 0.05). Conclusions Adolescents and young adults with T1D have evidence of microvascular dysfunction that can be detected using heat, a non-invasive physiologic stimulus. HbA1c appears to play an independent role in determining microvascular perfusion suggesting tight glycemic control is probably important for the development of vascular disease. PMID:25082568
Jordan, Lori C; Gindville, Melissa C; Scott, Allison O; Juttukonda, Meher R; Strother, Megan K; Kassim, Adetola A; Chen, Sheau-Chiann; Lu, Hanzhang; Pruthi, Sumit; Shyr, Yu; Donahue, Manus J
Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is to determine to what extent elevated oxygen extraction fraction may be uniquely present in patients with higher levels of clinical impairment and therefore may represent a candidate biomarker of stroke risk. Neurological evaluation, structural imaging, and the non-invasive T2-relaxation-under-spin-tagging magnetic resonance imaging method were applied in sickle cell anaemia (n = 34) and healthy race-matched control (n = 11) volunteers without sickle cell trait to assess whole-brain oxygen extraction fraction, cerebral blood flow, degree of vasculopathy, severity of anaemia, and presence of prior infarct; findings were interpreted in the context of physiological models. Cerebral blood flow and oxygen extraction fraction were elevated (P < 0.05) in participants with sickle cell anaemia (n = 27) not receiving monthly blood transfusions (interquartile range cerebral blood flow = 46.2-56.8 ml/100 g/min; oxygen extraction fraction = 0.39-0.50) relative to controls (interquartile range cerebral blood flow = 40.8-46.3 ml/100 g/min; oxygen extraction fraction = 0.33-0.38). Oxygen extraction fraction (P < 0.0001) but not cerebral blood flow was increased in participants with higher levels of clinical impairment. These data provide support for T2-relaxation-under-spin-tagging being able to quickly and non-invasively detect elevated oxygen extraction fraction in individuals with sickle cell anaemia with higher levels of clinical impairment. Our results support the
Mücke, Thomas; Rau, Andrea; Merezas, Andreas; Kanatas, Anastasios; Mitchell, David A; Wagenpfeil, Stefan; Wolff, Klaus-Dietrich; Steiner, Timm
Reconstruction with a free flap is routine in head and neck surgery. However, reliable assessment of perfusion can be difficult, so we prospectively evaluated it in 4 types of microvascular free flaps in the oral cavity (n=196) and assessed differences in blood flow by non-invasive monitoring with a laser Doppler flowmetry unit. We measured oxygen saturation, haemoglobin concentration, and velocity on the surface of the flap preoperatively at the donor site, and on the flap on the first, second, and seventh postoperative days, and after 4 weeks in 186/196 patients, mean (SD) age of 60 (13) years. We studied the radial forearm (n=76, 41%), fibular (n=45, 24%), anterolateral thigh (n=53, 28%), and soleus perforator (n=12, 7%) flaps. The values for the radial forearm flap differed significantly from the others. There were significant differences in haemoglobin concentrations between the fibular and soleus perforator flaps, and between the anterolateral thigh and soleus perforator flaps (p=0.002 each). Free flaps are unique in the way that perfusion develops after microvascular anastomoses. Knowledge of how each flap is perfused may indicate different patterns of healing that could potentially influence long term rehabilitation and detection of future deficits in perfusion.
Lindsey, Brooks D; Shelton, Sarah E; Martin, K Heath; Ozgun, Kathryn A; Rojas, Juan D; Foster, F Stuart; Dayton, Paul A
Mapping blood perfusion quantitatively allows localization of abnormal physiology and can improve understanding of disease progression. Dynamic contrast-enhanced ultrasound is a low-cost, real-time technique for imaging perfusion dynamics with microbubble contrast agents. Previously, we have demonstrated another contrast agent-specific ultrasound imaging technique, acoustic angiography, which forms static anatomical images of the superharmonic signal produced by microbubbles. In this work, we seek to determine whether acoustic angiography can be utilized for high resolution perfusion imaging in vivo by examining the effect of acquisition rate on superharmonic imaging at low flow rates and demonstrating the feasibility of dynamic contrast-enhanced superharmonic perfusion imaging for the first time. Results in the chorioallantoic membrane model indicate that frame rate and frame averaging do not affect the measured diameter of individual vessels observed, but that frame rate does influence the detection of vessels near and below the resolution limit. The highest number of resolvable vessels was observed at an intermediate frame rate of 3 Hz using a mechanically-steered prototype transducer. We also demonstrate the feasibility of quantitatively mapping perfusion rate in 2D in a mouse model with spatial resolution of ~100 μm. This type of imaging could provide non-invasive, high resolution quantification of microvascular function at penetration depths of several centimeters.
Ferreira, João C P; Fujihara, Caroline J; Fruhvald, Erika; Trevisol, Eduardo; Destro, Flavia C; Teixeira, Carlos R; Pantoja, José C F; Schmidt, Elizabeth M S; Palme, Rupert
Parrots kept in zoos and private households often develop psychological and behavioural disorders. Despite knowing that such disorders have a multifactorial aetiology and that chronic stress is involved, little is known about their development mainly due to a poor understanding of the parrots' physiology and the lack of validated methods to measure stress in these species. In birds, blood corticosterone concentrations provide information about adrenocortical activity. However, blood sampling techniques are difficult, highly invasive and inappropriate to investigate stressful situations and welfare conditions. Thus, a non-invasive method to measure steroid hormones is critically needed. Aiming to perform a physiological validation of a cortisone enzyme immunoassay (EIA) to measure glucocorticoid metabolites (GCM) in droppings of 24 Blue-fronted parrots (Amazona aestiva), two experiments were designed. During the experiments all droppings were collected at 3-h intervals. Initially, birds were sampled for 24 h (experiment 1) and one week later assigned to four different treatments (experiment 2): Control (undisturbed), Saline (0.2 mL of 0.9% NaCl IM), Dexamethasone (1 mg/kg IM) and Adrenocorticotropic hormone (ACTH; 25 IU IM). Treatments (always one week apart) were applied to all animals in a cross-over study design. A daily rhythm pattern in GCM excretion was detected but there were no sex differences (first experiment). Saline and dexamethasone treatments had no effect on GCM (not different from control concentrations). Following ACTH injection, GCM concentration increased about 13.1-fold (median) at the peak (after 3-9 h), and then dropped to pre-treatment concentrations. By a successful physiological validation, we demonstrated the suitability of the cortisone EIA to non-invasively monitor increased adrenocortical activity, and thus, stress in the Blue-fronted parrot. This method opens up new perspectives for investigating the connection between behavioural
Ferreira, João C. P.; Fujihara, Caroline J.; Fruhvald, Erika; Trevisol, Eduardo; Destro, Flavia C.; Teixeira, Carlos R.; Pantoja, José C. F.; Schmidt, Elizabeth M. S.; Palme, Rupert
Parrots kept in zoos and private households often develop psychological and behavioural disorders. Despite knowing that such disorders have a multifactorial aetiology and that chronic stress is involved, little is known about their development mainly due to a poor understanding of the parrots’ physiology and the lack of validated methods to measure stress in these species. In birds, blood corticosterone concentrations provide information about adrenocortical activity. However, blood sampling techniques are difficult, highly invasive and inappropriate to investigate stressful situations and welfare conditions. Thus, a non-invasive method to measure steroid hormones is critically needed. Aiming to perform a physiological validation of a cortisone enzyme immunoassay (EIA) to measure glucocorticoid metabolites (GCM) in droppings of 24 Blue-fronted parrots (Amazona aestiva), two experiments were designed. During the experiments all droppings were collected at 3-h intervals. Initially, birds were sampled for 24 h (experiment 1) and one week later assigned to four different treatments (experiment 2): Control (undisturbed), Saline (0.2 mL of 0.9% NaCl IM), Dexamethasone (1 mg/kg IM) and Adrenocorticotropic hormone (ACTH; 25 IU IM). Treatments (always one week apart) were applied to all animals in a cross-over study design. A daily rhythm pattern in GCM excretion was detected but there were no sex differences (first experiment). Saline and dexamethasone treatments had no effect on GCM (not different from control concentrations). Following ACTH injection, GCM concentration increased about 13.1-fold (median) at the peak (after 3–9 h), and then dropped to pre-treatment concentrations. By a successful physiological validation, we demonstrated the suitability of the cortisone EIA to non-invasively monitor increased adrenocortical activity, and thus, stress in the Blue-fronted parrot. This method opens up new perspectives for investigating the connection between behavioural
Stauffer, Paul R.; Maccarini, Paolo F.; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K.; Bardati, Fernando; Tognolatti, Piero; Snow, Brent
Background Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. Methods We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon “kidney” implanted 3–4cm deep in thorax and varied 2–6°C from core temperature. Results SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40–44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2–6°C changes of 30mL “kidney” targets at depth in 34°C invivo pig thorax. Conclusion A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects ≥2°C rise in 30mL “urine” located 3–4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4–5 reflux of warmed urine for non-invasive detection of VUR. PMID:22866211
Vogel, A; Chernomordik, V; Riley, J; Hassan, M; Amyot, F; Dasgeb, B; Demos, S G; Pursley, R; Little, R; Yarchoan, R; Tao, Y; Gandjbakhche, A H
This research describes a non-invasive, non-contact method used to quantitatively analyze the functional characteristics of tissue. Multi-spectral images collected at several near-infrared wavelengths are input into a mathematical optical skin model that considers the contributions from different analytes in the epidermis and dermis skin layers. Through a reconstruction algorithm, we can quantify the percent of blood in a given area of tissue and the fraction of that blood that is oxygenated. Imaging normal tissue confirms previously reported values for the percent of blood in tissue and the percent of blood that is oxygenated in tissue and surrounding vasculature, for the normal state and when ischemia is induced. This methodology has been applied to assess vascular Kaposi's sarcoma lesions and the surrounding tissue before and during experimental therapies. The multi-spectral imaging technique has been combined with laser Doppler imaging to gain additional information. Results indicate that these techniques are able to provide quantitative and functional information about tissue changes during experimental drug therapy and investigate progression of disease before changes are visibly apparent, suggesting a potential for them to be used as complementary imaging techniques to clinical assessment.
Le, Yuan; Stein, Ashley; Berry, Colin; Kellman, Peter; Bennett, Eric E; Taylor, Joni; Lucas, Katherine; Kopace, Rael; Chefd'Hotel, Christophe; Lorenz, Christine H; Croisille, Pierre; Wen, Han
The purpose of this study is to develop and evaluate a displacement-encoded pulse sequence for simultaneous perfusion and strain imaging. Displacement-encoded images in two to three myocardial slices were repeatedly acquired using a single-shot pulse sequence for 3 to 4 min, which covers a bolus infusion of Gadolinium contrast. The magnitudes of the images were T(1) weighted and provided quantitative measures of perfusion, while the phase maps yielded strain measurements. In an acute coronary occlusion swine protocol (n = 9), segmental perfusion measurements were validated against microsphere reference standard with a linear regression (slope 0.986, R(2) = 0.765, Bland-Altman standard deviation = 0.15 mL/min/g). In a group of ST-elevation myocardial infarction patients (n = 11), the scan success rate was 76%. Short-term contrast washout rate and perfusion are highly correlated (R(2) = 0.72), and the pixelwise relationship between circumferential strain and perfusion was better described with a sigmoidal Hill curve than linear functions. This study demonstrates the feasibility of measuring strain and perfusion from a single set of images.
Le, Yuan; Stein, Ashley; Berry, Colin; Kellman, Peter; Bennett, Eric E.; Taylor, Joni; Lucas, Katherine; Kopace, Rael; Chefd’Hotel, Christophe; Lorenz, Christine H.; Croisille, Pierre; Wen, Han
The purpose of this study is to develop and evaluate a displacement-encoded pulse sequence for simultaneous perfusion and strain imaging. Displacement-encoded images in 2–3 myocardial slices were repeatedly acquired using a single shot pulse sequence for 3 to 4 minutes, which covers a bolus infusion of Gd. The magnitudes of the images were T1 weighted and provided quantitative measures of perfusion, while the phase maps yielded strain measurements. In an acute coronary occlusion swine protocol (n=9), segmental perfusion measurements were validated against microsphere reference standard with a linear regression (slope 0.986, R2 = 0.765, Bland-Altman standard deviation = 0.15 ml/min/g). In a group of ST-elevation myocardial infarction(STEMI) patients (n=11), the scan success rate was 76%. Short-term contrast washout rate and perfusion are highly correlated (R2=0.72), and the pixel-wise relationship between circumferential strain and perfusion was better described with a sigmoidal Hill curve than linear functions. This study demonstrates the feasibility of measuring strain and perfusion from a single set of images. PMID:20544714
Ross, Michael P.
A coaxial hyperthermia applicator for applying non-invasively electromagnetic energy to a body against which it is placed. The coaxial applicator antenna has formed integrally within it a non-invasive radiometric antenna for receiving thermoelectromagnetic emissions. The coaxial-configured applicator produces a bell-shaped radiation pattern symmetric about the axis of symmetry of the coaxial applicator. Integrating the radiometric antenna within the coaxial applicator produces a single device that performs dual functions. The first function is to transmit non-invasively energy for heating a subcutaneous tumor. The second function is to receive non-invasively thermal electromagnetic radiation from the tumor by which temperature is sensed and fed back to control the output of the coaxial applicator.
A coaxial hyperthermia applicator is disclosed for applying non-invasively electromagnetic energy to a body against which it is placed. The coaxial applicator antenna has formed integrally within it a non-invasive radiometric antenna for receiving thermoelectromagnetic emissions. The coaxial-configured applicator produces a bell-shaped radiation pattern symmetric about the axis of symmetry of the coaxial applicator. Integrating the radiometric antenna within the coaxial applicator produces a single device that performs dual functions. The first function is to transmit non-invasively energy for heating a subcutaneous tumor. The second function is to receive non-invasively thermal electromagnetic radiation from the tumor by which temperature is sensed and fed back to control the output of the coaxial applicator. 11 figs.
Cancer is a leading cause of death worldwide. It remains the second most common cause of death in the US, accounting for nearly 1 out of every 4 deaths. Improved fundamental understanding of molecular processes and pathways resulting in cancer development has catalyzed a shift towards molecular analysis of cancer using imaging technologies. It is expected that the non-invasive or minimally invasive molecular imaging analysis of cancer can significantly aid in improving the early detection of cancer and will result in reduced mortality and morbidity associated with the disease. The central hypothesis of the proposed research is that non-invasive imaging of changes in metabolic activity of individual cells, and extracellular pH within a tissue will improve early stage detection of cancer. The specific goals of this research project were to: (a) develop novel optical imaging probes to image changes in choline metabolism and tissue pH as a function of progression of cancer using clinically isolated tissue biopsies; (b) correlate changes in tissue extracellular pH and metabolic activity of tissues as a function of disease state using clinically isolated tissue biopsies; (c) provide fundamental understanding of relationship between tumor hypoxia, acidification of the extracellular space and altered cellular metabolism with progression of cancer. Three novel molecular imaging probes were developed to detect changes in choline and glucose metabolism and extracellular pH in model systems and clinically isolated cells and biopsies. Glucose uptake and metabolism was measured using a fluorescence analog of glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose), while choline metabolism was measured using a click chemistry analog of choline, propargyl choline, which can be in-situ labeled with a fluorophore Alexa-488 azide via a click chemistry reaction. Extracellular pH in tissue were measured by Alexa-647 labeled pHLIP (pH low insertion peptide
Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.
Dynamic cardiac CT perfusion (CTP) is a high resolution, non-invasive technique for assessing myocardial blood ow (MBF), which in concert with coronary CT angiography enable CT to provide a unique, comprehensive, fast analysis of both coronary anatomy and functional ow. We assessed perfusion in a porcine model with and without coronary occlusion. To induce occlusion, each animal underwent left anterior descending (LAD) stent implantation and angioplasty balloon insertion. Normal ow condition was obtained with balloon completely de ated. Partial occlusion was induced by balloon in ation against the stent with FFR used to assess the extent of occlusion. Prospective ECG-triggered partial scan images were acquired at end systole (45% R-R) using a multi-detector CT (MDCT) scanner. Images were reconstructed using FBP and a hybrid iterative reconstruction (iDose4, Philips Healthcare). Processing included: beam hardening (BH) correction, registration of image volumes using 3D cubic B-spline normalized mutual-information, and spatio-temporal bilateral ltering to reduce partial scan artifacts and noise variation. Absolute blood ow was calculated with a deconvolutionbased approach using singular value decomposition (SVD). Arterial input function was estimated from the left ventricle (LV) cavity. Regions of interest (ROIs) were identi ed in healthy and ischemic myocardium and compared in normal and occluded conditions. Under-perfusion was detected in the correct LAD territory and ow reduction agreed well with FFR measurements. Flow was reduced, on average, in LAD territories by 54%.
CBF and related parameters were studied in 68 patients before, during, and following cardiopulmonary bypass. CBF was measured using the intraarterial 133Xe injection method. The extracorporeal circuit was nonpulsatile with a bubble oxygenator administering 3-5% CO2 in the main group of hypercapnic patients (n = 59) and no CO2 in a second group of hypocapnic patients. In the hypercapnic patients, marked changes in CBF occurred during bypass. Evidence was found of a brain luxury perfusion that could not be related to the effect of CO2 per se. Mean CBF was 29 ml/100 g/min just before bypass, 49 ml/100 g/min at steady-state hypothermia (27 degrees C), reached a maximum of 73 ml/100 g/min during the rewarming phase (32 degrees C), fell to 56 ml/100 g/min at steady-state normothermic bypass (37 degrees C), and was 48 ml/100 g/min shortly after bypass was stopped. Addition of CO2 evoked systemic vasodilation with low blood pressure and a rebound hyperemia. The hypocapnic group responded more physiologically to the induced changes in hematocrit (Htc) and temperature, CBF being 25, 23, 25, 34, and 35 ml/100 g/min, respectively, during the five corresponding periods. Carbon dioxide was an important regulator of CBF during all phases of cardiac surgery, the responsiveness of CBF being approximately 4% for each 1-mm Hg change of PaCO2. The level of MABP was important for the CO2 response. At low blood pressure states, the CBF responsiveness to changes in PaCO2 was almost abolished. An optimal level of PaCO2 during hypothermic bypass of approximately 25 mm Hg (at actual temperature) is recommended. A normal autoregulatory response of CBF to changes in blood pressure was found during and following bypass. The lower limit of autoregulation was at pressure levels of approximately 50-60 mm Hg. CBF autoregulation was almost abolished at PaCO2 levels of greater than 50 mm Hg. The degree of hemodilution neither affected the CO2 response nor impaired CBF autoregulation, although, as
Collings, Shaun; Thompson, Oliver; Hirst, Evan; Goossens, Louise; George, Anup; Weinkove, Robert
Background and Aims Anaemia is a major health burden worldwide. Although the finding of conjunctival pallor on clinical examination is associated with anaemia, inter-observer variability is high, and definitive diagnosis of anaemia requires a blood sample. We aimed to detect anaemia by quantifying conjunctival pallor using digital photographs taken with a consumer camera and a popular smartphone. Our goal was to develop a non-invasive screening test for anaemia. Patients and Methods The conjunctivae of haemato-oncology in- and outpatients were photographed in ambient lighting using a digital camera (Panasonic DMC-LX5), and the internal rear-facing camera of a smartphone (Apple iPhone 5S) alongside an in-frame calibration card. Following image calibration, conjunctival erythema index (EI) was calculated and correlated with laboratory-measured haemoglobin concentration. Three clinicians independently evaluated each image for conjunctival pallor. Results Conjunctival EI was reproducible between images (average coefficient of variation 2.96%). EI of the palpebral conjunctiva correlated more strongly with haemoglobin concentration than that of the forniceal conjunctiva. Using the compact camera, palpebral conjunctival EI had a sensitivity of 93% and 57% and specificity of 78% and 83% for detection of anaemia (haemoglobin < 110 g/L) in training and internal validation sets, respectively. Similar results were found using the iPhone camera, though the EI cut-off value differed. Conjunctival EI analysis compared favourably with clinician assessment, with a higher positive likelihood ratio for prediction of anaemia. Conclusions Erythema index of the palpebral conjunctiva calculated from images taken with a compact camera or mobile phone correlates with haemoglobin and compares favourably to clinician assessment for prediction of anaemia. If confirmed in further series, this technique may be useful for the non-invasive screening for anaemia. PMID:27070544
Ueno, Toshiaki; Ballard, Richard E.; Macias, Brandon R.; Yost, William T.; Hargens, Alan R.
INTRODUCTION: Intracranial pressure (ICP) may play a significant role in physiological responses to microgravity by contributing to the nausea associated with microgravity exposure. However, effects of altered gravity on ICP in astronauts have not been investigated, primarily due to the invasiveness of currently available techniques. We have developed an ultrasonic device that monitors changes in cranial diameter pulsation non-invasively so that we can evaluate ICP dynamics in astronauts during spaceflight. This study was designed to demonstrate the feasibility of our ultrasound technique under the physiological condition in which ICP dynamics are changed due to altered gravitational force. METHODS: Six healthy volunteers were placed at 60 degrees head-up, 30 degrees headup, supine, and 15 degrees head-down positions for 3 min at each angle. We measured arterial blood pressure (ABP) with a finger pressure cuff, and cranial diameter pulsation with a pulsed phase lock loop device (PPLL). RESULTS: Analysis of covariance demonstrated that amplitudes of cranial diameter pulsations were significantly altered with the angle of tilt (p < 0.001). The 95% confidence interval for linear regression coefficients of the cranial diameter pulsation amplitudes with tilt angle was 0.862 to 0.968. However, ABP amplitudes did not show this relationship. DISCUSSION: Our noninvasive ultrasonic technique reveals that the amplitude of cranial diameter pulsation decreases as a function of tilt angle, suggesting that ICP pulsation follows the same relationship. It is demonstrated that the PPLL device has a sufficient sensitivity to detect changes non-invasively in ICP pulsation caused by altered gravity.
Taha, A; Grant, V; Kelly, R
Background and aims: Given its role in mediating inflammation, the use of urinary interleukin-8 (IL-8) was assessed in the non-invasive diagnosis of acute and chronic inflammatory diseases. Methods: IL-8 was measured by an enzyme linked immunosorbent assay in random urine samples (1 ml each) carrying code numbers and taken from 208 patients: 177 adults and 31 children presenting with a range of active or inactive inflammatory conditions. Results: In the appropriate controls and in patients with inactive inflammation, the median urinary IL-8 levels ranged from 7–12 pg/ml, compared with 104 pg/ml in active ulcerative colitis (p = 0.002), 54 in active Crohn's disease (p = 0.025), 93 in active rheumatoid arthritis (p = 0.001), 107 in acute cholecystitis (p<0.0001), 127 in acute appendicitis (p = 0.0001), and 548 pg/ml in urinary tract infection (p<0.0001). Children with non-viral inflammation/infection also had higher IL-8 values (median, 199 pg/ml; p = 0.0001) than those with viral infection (median, 7 pg/ml) or non-specific conditions (median, 10 pg/ml). In the study group as a whole urinary IL-8 values correlated positively with peripheral blood white cell count (r = 0.32; p < 0.001), erythrocyte sedimentation rate (r = 0.41; p<0.001), and C-reactive protein (r = 0.33; p<0.001). Conclusion: Taking the appropriate clinical situation into account, urinary IL-8 measurement helps in the non-invasive assessment of active inflammation in at least a number of common acute and chronic conditions. PMID:12697917
Kacprzak, Michal; Skora, A.; Obidzinska, J.; Zbiec, A.; Maniewski, Roman; Staszkiewicz, W.
The laser Doppler method offers a non-invasive, real time technique for monitoring of blood perfusion in microcirculation. In practical measurements the perfusion index is given only in relative values. Thus, accurate and reproducible results can be only obtained when using a well controlled stimulation test. The aim of this study was evaluation of the thermal stimulation test, which is frequently used to investigate microcirculation in patients with Raynaud's syndrome. Three types of thermal tests, in which air or water with temperature in range 5°C - 40°C were used. Ten normal volunteers and fifteen patients with clinical symptoms of the primary Raynaud's syndrome were enrolled in this study. To estimate skin microcirculation changes during the thermal test, the multichannel laser Doppler system and laser Doppler scanner were used. The obtained results were analyzed from the point of view of the efficiency of these methods and the thermal provocative tests in differentiation of normal subjects and patient with Raynaud's syndrome.
Kalam, Mohd Abul; Khan, Abdul Arif; Alshamsan, Aws
Polymeric nanoparticulate carriers play an important role and holding a significant potential for the development of novel immunomodulatory agents as easily they are taken up by antigen presenting cells. They allow an enhanced antigen stability, better immunogenicity and immunostimulatory effect with sustained and controlled release of the antigen to the target sites. Better information and vital understanding of mechanism of action, interaction of such vectors with the APCs and dendritic cells and antigen release kinetics in immunomodulatory effects, and improved knowledge of their in vivo fate and distribution are now needed, those collectively would speed up the rational strategies of nanoparticles as carriers for vaccines and other protein antigens. The evolution of such innovative adjuvants for protein and DNA immunizations are an exciting and growing zone in immunology, which may enhance the clinical outcomes in many infectious and non-infectious diseases. This review summarizes the recent advances in nano-vaccinology with polymeric (especially biodegradable) carriers, their methods of preparation, surface modification, their interaction with antigen presenting cells, release of antigens, its kinetics and mechanism in the delivery of vaccines via non-invasive routes. PMID:28123631
Vrijsen, Bart; Testelmans, Dries; Belge, Catharina; Robberecht, Wim; Van Damme, Philip; Buyse, Bertien
Abstract Non-invasive ventilation (NIV) is widely used to improve alveolar hypoventilation in amyotrophic lateral sclerosis. Several studies indicate a better survival when NIV is used, certainly in patients with none to moderate bulbar dysfunction. Data on quality of life (QoL) are rather disputable. Overall QoL is shown to be equivalent in patients with or without NIV, although health-related QoL is shown to be increased in patients with none to moderate bulbar dysfunction. NIV improves sleep quality, although patient-ventilator asynchronies are demonstrated. FVC < 50%, seated or supine, has been widely applied as threshold to initiate NIV. Today, measurements of respiratory muscle strength, nocturnal gas exchange and symptomatic complaints are used as indicators to start NIV. Being compliant with NIV therapy increases QoL and survival. Cough augmentation has an important role in appropriate NIV. Patients have today more technical options and patients with benefit from these advances are growing in number. Tracheal ventilation needs to be discussed when NIV seems impossible or becomes insufficient.
Soresi, Maurizio; Giannitrapani, Lydia; Cervello, Melchiorre; Licata, Anna; Montalto, Giuseppe
Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis. Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications. They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores. Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US Doppler, contrast enhanced US and Elastography. US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis, in this case Elastography is more reliable. This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis. PMID:25561782
Tooley, Katie L; Howarth, Gordon S; Butler, Ross N
Mucositis is a common and debilitating side effect of chemotherapy that manifests due to the inability of chemotherapy agents to discriminate between normal and neoplastic cells. This results in ulcerating lesions lining the gastrointestinal tract. Moreover, the development of efficacious treatments for small intestinal mucositis has been hindered as the pathobiology of mucositis is still not fully understood. The small intestine is an extensive organ which is largely inaccessible by conventional means. Non-invasive biomarkers such as small intestinal permeability, H(2) breath tests, serum citrulline tests and the (13)C-sucrose breath test (SBT) have emerged as potential markers of small intestinal function. The SBT is emerging as the more appropriate biomarker to assess chemotherapy-induced mucositis in cancer patients and animal models, where it measures the decrease in sucrase activity associated with villus blunting and crypt disruption. The SBT has been successfully applied to detect mucositis induced by different classes of chemotherapy agents and has been used successfully to monitor small intestinal function with a range of candidate anti-mucositis treatments. We propose the SBT a superior biomarker of small intestinal function that could be successfully applied in clinical practice for monitoring the development of mucositis in cancer patients undergoing chemotherapy.
Chawke, Caroline; Kanai, Ryota
People generally have imperfect introspective access to the mechanisms underlying their political beliefs, yet can confidently communicate the reasoning that goes into their decision making process. An innate desire for certainty and security in ones beliefs may play an important and somewhat automatic role in motivating the maintenance or rejection of partisan support. The aim of the current study was to clarify the role of the DLPFC in the alteration of political beliefs. Recent neuroimaging studies have focused on the association between the DLPFC (a region involved in the regulation of cognitive conflict and error feedback processing) and reduced affiliation with opposing political candidates. As such, this study used a method of non-invasive brain simulation (tRNS) to enhance activity of the bilateral DLPFC during the incorporation of political campaign information. These findings indicate a crucial role for this region in political belief formation. However, enhanced activation of DLPFC does not necessarily result in the specific rejection of political beliefs. In contrast to the hypothesis the results appear to indicate a significant increase in conservative values regardless of participant's initial political orientation and the political campaign advertisement they were exposed to.
Blanchard, D; Diebold, B; Peronneau, P; Foult, J M; Nee, M; Guermonprez, J L; Maurice, P
The value of Doppler echocardiography for the non-invasive diagnosis of mitral regurgitation was studied blindly in 161 consecutive invasively investigated adult patients. Regurgitation was graded from 0 to 3 at selective left ventricular angiography. The Doppler echocardiographic examination was considered to be positive when a disturbed systolic flow was found within the left atrium behind the aorta or the anterior leaflet of the mitral valve. The test was considered to be negative in the absence of a regurgitant jet. The level of the signal to noise ratio was checked by the recording of the ventricular filling flow. The study was performed in 131 cases from the left side of the sternum and in 101 cases from the apex. There were no false positives and thus the specificity was 100 per cent. The 20 false negatives were all in patients with grade 1 regurgitation. Thus only some (33%) instances of mild regurgitation were misdiagnosed, and the sensitivity for moderate to severe mitral regurgitation was 100 per cent. PMID:7236465
Armstrong, Neil; Fawkner, Samantha G
Oded Bar-Or's hypothesis that children may be "metabolic non-specialists", even when engaging in specialized sports, has stimulated the study of paediatric exercise metabolism since the publication of his classic text Pediatric sports medicine for the practitioner in 1983. Evidence drawn from several methodologies indicates an interplay of anaerobic and aerobic exercise metabolism in which children have a relatively higher metabolic contribution from oxidative energy pathways than adolescents or adults, whereas there is a progressive increase in glycolytic support of exercise with age, at least into adolescence and possibly into young adulthood. The picture is generally consistent but incomplete, as research with young people has been limited by both ethical and methodological constraints. The recent rigorous introduction of non-invasive techniques such as breath-by-breath respiratory gas analysis and magnetic resonance spectroscopy into paediatric exercise physiology promises to open up new avenues of research and generate unique insights into the metabolism of the exercising muscle during growth and maturation. It therefore appears that we might have available the tools necessary to answer some of the elegant questions raised by Professor Bar-Or over 25 years ago.
Ueno, Toshiaki; Ballard, R. E.; Yost, W. T.; Hargens, A. R.
Exposure to microgravity causes a cephalad fluid shift which may elevate intracranial pressure (ICP). Elevation in ICP may affect cerebral hemodynamics in astronauts during space flight. ICP is, however, a difficult parameter to measure due to the invasiveness of currently available techniques. We already reported our development of a non-invasive ultrasound device for measurement of ICP. We recently modified the device so that we might reproducibly estimate ICP changes in association with cardiac cycles. In the first experiment, we measured changes in cranial distance with the ultrasound device in cadavera while changing ICP by infusing saline into the lateral ventricle. In the second experiment, we measured changes in cranial distance in five healthy volunteers while placing them in 60 deg, 30 deg head-up tilt, supine, and 10 deg head-down tilt position. In the cadaver study, fast Fourier transformation revealed that cranial pulsation is clearly associated with ICP pulsation. The ratio of cranial distance and ICP pulsation is 1.3microns/mmHg. In the tilting study, the magnitudes of cranial pulsation are linearly correlated to tilt angles (r=0.87). The ultrasound device has sufficient sensitivity to detect cranial pulsation in association with cardiac cycles. By analyzing the magnitude of cranial pulsation, estimates of ICP during space flight are possible.
de Franchis, Roberto
Current guidelines recommend screening all cirrhotic patients by endoscopy, to identify patients at risk of bleeding who should undergo prophylactic treatment. However, since the prevalence of varices in cirrhotic patients is variable, universal screening would imply a large number of unnecessary endoscopies and a heavy burden for endoscopy units. In addition, compliance to screening programs may be hampered by the perceived unpleasantness of endoscopy. Predicting the presence of oesophageal varices by non-invasive means might increase compliance and would permit to restrict the performance of endoscopy to those patients with a high probability of having varices. Over the years, several studies have addressed this issue by assessing the potential of biochemical, clinical and ultrasound parameters, transient elastography, CT scanning and video capsule endoscopy. The platelet count/spleen diameter ratio, CT scanning and video capsule endoscopy have shown promising performance characteristics, although none of them is equivalent to EGD. These methods are perceived by patients as preferable to endoscopy and thus might increase adherence to screening programs. Whether this will compensate for the lower sensitivity of these alternative techniques, and ultimately improve the outcomes if more patients undergo screening, is the crucial question that will have to be answered in the future.
Mizushina, S; Shimizu, T; Sugiura, T
The present status of the development of a non-invasive thermometer based on microwave radiometry at our laboratory is reported. We have developed a model fitting technique combined with a Monte Carlo technique to retrieve temperature-depth profiles from multi (4-6)-frequency-band microwave radiometric data along with confidence intervals (2-sigma) of tissue temperatures as a function of depth. In order to make the radiometric technique compatible with the heating, brightness temperatures are measured through a 1 cm thick water bolus. Results of phantom experiments are presented to demonstrate the above capabilities of the method. Numerical simulation studies have shown that 2-sigma intervals would be 1.0 K or less over a 0-4 cm range and 1.4 K at 5 cm from the surface with using a six-band, 1-5 GHz radiometer having brightness temperature resolution of 0.03 K (3 s integration time). The six-band instrument is currently being assembled at our laboratory.
Lademann, J.; Patzelt, A.; Darvin, M.; Richter, H.; Antoniou, C.; Sterry, W.; Koch, S.
In the present paper the application of optical non-invasive methods in dermatology and cosmetology is discussed. Laser scanning microscopy (LSM) and optical coherent tomography (OCT) are the most promising methods for this application. Using these methods, the analysis of different skin parameters like dryness and oiliness of the skin, the barrier function and the structure of furrows and wrinkles are discussed. Additionally the homogeneity of distribution of topically applied creams, as well as their penetration into the skin were investigated. It is shown that these methods are highly valuable in dermatology for diagnostic and therapy control and for basic research, for instance in the field of structure analysis of hair follicles and sweat glands. The vertical images of the tissue produced by OCT can be easily compared with histological sections. Unfortunately, the resolution of the OCT technique is not high enough to carry out measurements on a cellular level, as is possible by LSM. LSM has the advantage that it can be used for the investigation of penetration and storage processes of topically applied substances, if these substances have fluorescent properties or if they are fluorescent-labelled.
Dambacher, Franziska; Schuhmann, Teresa; Lobbestael, Jill; Arntz, Arnoud; Brugman, Suzanne; Sack, Alexander T
Aggressive behavior poses a threat to human collaboration and social safety. It is of utmost importance to identify the functional mechanisms underlying aggression and to develop potential interventions capable of reducing dysfunctional aggressive behavior already at a brain level. We here experimentally shifted fronto-cortical asymmetry to manipulate the underlying motivational emotional states in both male and female participants while assessing the behavioral effects on proactive and reactive aggression. Thirty-two healthy volunteers received either anodal transcranial direct current stimulation to increase neural activity within right dorsolateral prefrontal cortex, or sham stimulation. Aggressive behavior was measured with the Taylor Aggression Paradigm. We revealed a general gender effect, showing that men displayed more behavioral aggression than women. After the induction of right fronto-hemispheric dominance, proactive aggression was reduced in men. This study demonstrates that non-invasive brain stimulation can reduce aggression in men. This is a relevant and promising step to better understand how cortical brain states connect to impulsive actions and to examine the causal role of the prefrontal cortex in aggression. Ultimately, such findings could help to examine whether the brain can be a direct target for potential supportive interventions in clinical settings dealing with overly aggressive patients and/or violent offenders.
Mustafaev, Aleksandr; Rastvorova, Iuliia; Khobnya, Kristina; Podenko, Sofia
The analysis of biomarkers can help to identify the significant number of diseases: lung cancer, tuberculosis, diabetes, high levels of stress, psychosomatic disorders etc. To implement continuous monitoring of the state of human health, compact VUV photoionization detector with current-voltage measurement is designed by Saint-Petersburg Mining University Plasma Research Group. This sensor is based on the patented method of stabilization of electric parameters - CES (Collisional Electron Spectroscopy). During the operation at atmospheric pressure VUV photoionization sensor measures the energy of electrons, produced in the ionization with the resonance photons, whose wavelength situated in the vacuum ultraviolet (VUV). A special software was developed to obtain the second-order derivative of the I-U characteristics, taken by the VUV sensor, to construct the energy spectra of the characteristic electrons. VUV photoionization detector has an unique set of parameters: small size (10*10*1 mm), low cost, wide range of recognizable molecules, as well as accuracy, sufficient for using this instrument for the medical purposes. This device can be used for non-invasive medical diagnostics without compromising the quality of life, for control of environment and human life. Work supported by Foundation for Assistance to Small Innovative Enterprises in Science and Technology.
Soresi, Maurizio; Giannitrapani, Lydia; Cervello, Melchiorre; Licata, Anna; Montalto, Giuseppe
Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis. Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications. They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores. Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US Doppler, contrast enhanced US and Elastography. US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis, in this case Elastography is more reliable. This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis.
Bolognini, Nadia; Maravita, Angelo
Most of current knowledge about the mechanisms of multisensory integration of environmental stimuli by the human brain derives from neuroimaging experiments. However, neuroimaging studies do not always provide conclusive evidence about the causal role of a given area for multisensory interactions, since these techniques can mainly derive correlations between brain activations and behavior. Conversely, techniques of non-invasive brain stimulation (NIBS) represent a unique and powerful approach to inform models of causal relations between specific brain regions and individual cognitive and perceptual functions. Although NIBS has been widely used in cognitive neuroscience, its use in the study of multisensory processing in the human brain appears a quite novel field of research. In this paper, we review and discuss recent studies that have used two techniques of NIBS, namely transcranial magnetic stimulation and transcranial direct current stimulation, for investigating the causal involvement of unisensory and heteromodal cortical areas in multisensory processing, the effects of multisensory cues on cortical excitability in unisensory areas, and the putative functional connections among different cortical areas subserving multisensory interactions. The emerging view is that NIBS is an essential tool available to neuroscientists seeking for causal relationships between a given area or network and multisensory processes. With its already large and fast increasing usage, future work using NIBS in isolation, as well as in conjunction with different neuroimaging techniques, could substantially improve our understanding of multisensory processing in the human brain.
Malerba, M; Montuschi, P
Cigarette smoking is the most important risk factor for the development of chronic obstructive pulmonary disease (COPD) and lung cancer, but only a part of smoking subjects develop these respiratory pathologies. Therefore, it is necessary to find sensible parameters to detect early lung alterations due to chronic tobacco smoke exposure. Long-term cigarette smoking is associated with a persistent inflammatory response in the lung that leads to tissue injury and dysfunction. Bronchoscopy and bronchial biopsies are the gold standard techniques for assessing pulmonary inflammation, but are invasive and not routinely used. Cellular analysis of induced sputum and measurement of fraction of exhaled nitric oxide (F(E)NO) are validated non-invasive techniques for assessing respiratory inflammation. Measurement of biomolecules in sputum supernatants and exhaled breath condensate (EBC) are used as a research tool, but require standardization of procedures and, generally, analytical validation. Electronic nose differentiates healthy smokers from healthy nonsmokers based on breath volatile organic compounds (VOC) patterns. These techniques are potentially useful for identifying biomarkers of pulmonary inflammation and oxidative stress. Induced sputum, F(E)NO, EBC and electronic nose are suitable for longitudinal sampling, thereby facilitating monitoring of lung damage process. This approach could enable an early identification of subgroups of healthy smokers at higher risk for tobacco-induced lung damage and prompt planning of secondary prevention strategies.
Chawke, Caroline; Kanai, Ryota
People generally have imperfect introspective access to the mechanisms underlying their political beliefs, yet can confidently communicate the reasoning that goes into their decision making process. An innate desire for certainty and security in ones beliefs may play an important and somewhat automatic role in motivating the maintenance or rejection of partisan support. The aim of the current study was to clarify the role of the DLPFC in the alteration of political beliefs. Recent neuroimaging studies have focused on the association between the DLPFC (a region involved in the regulation of cognitive conflict and error feedback processing) and reduced affiliation with opposing political candidates. As such, this study used a method of non-invasive brain simulation (tRNS) to enhance activity of the bilateral DLPFC during the incorporation of political campaign information. These findings indicate a crucial role for this region in political belief formation. However, enhanced activation of DLPFC does not necessarily result in the specific rejection of political beliefs. In contrast to the hypothesis the results appear to indicate a significant increase in conservative values regardless of participant's initial political orientation and the political campaign advertisement they were exposed to. PMID:26834603
Karathanasis, Efstathios; Park, Jaekeun; Agarwal, Abhiruchi; Patel, Vijal; Zhao, Fuqiang; Annapragada, Ananth V.; Hu, Xiaoping; Bellamkonda, Ravi V.
Nanocarrier mediated therapy of gliomas has shown promise. The success of systemic nanocarrier-based chemotherapy is critically dependent on the so-called leaky vasculature to permit drug extravasation across the blood-brain barrier. Yet, the extent of vascular permeability in individual tumors varies widely, resulting in a correspondingly wide range of responses to the therapy. However, there exist no tools currently for rationally determining whether tumor blood vessels are amenable to nanocarrier mediated therapy in an individualized, patient specific manner today. To address this need for brain tumor therapy, we have developed a multifunctional 100 nm scale liposomal agent encapsulating a gadolinium-based contrast agent for contrast-enhanced magnetic resonance imaging with prolonged blood circulation. Using a 9.4 T MRI system, we were able to track the intratumoral distribution of the gadolinium-loaded nanocarrier in a rat glioma model for a period of three days due to improved magnetic properties of the contrast agent being packaged in a nanocarrier. Such a nanocarrier provides a tool for non-invasively assessing the suitability of tumors for nanocarrier mediated therapy and then optimizing the treatment protocol for each individual tumor. Additionally, the ability to image the tumor in high resolution can potentially constitute a surgical planning tool for tumor resection.
ZHANG, JIAO; ZHANG, BIN
The aim of the present study was to evaluate the efficacy of using non-invasive DNA testing technology in screening Down's syndrome among women of advanced maternal age (AMA) and to provide evidence for prenatal screening of Down's syndrome. With a double-blind design, 8 ml of peripheral venous blood samples were collected from 87 women aged ≥35 years after 12 weeks of pregnancy. All cases were recorded with unique identification cards with clinical details and followed up until delivery. All the non-invasive prenatal testing results were confirmed by amniotic fluid fetal karyotyping (the gold standard of aneuploidy test), follow-up examination by neonatologists or neonatal blood karyotyping. The sensitivity, specificity and other indicators of non-invasive DNA testing technology were calculated based on the data of 87 women of AMA. Among the 87 women of AMA, 5 were cases with abnormal numbers of chromosomes (3 cases of trisomy 21, 1 case of trisomy 18 and 1 case of 47, XXX). The sensitivity and specificity reached 100% for trisomy 21, trisomy 18 and 47, XXX. The present study supports that non-invasive DNA testing is a useful method of AMA screening of Down's syndrome with 100% accuracy. Therefore, it can be used as an important alternative screening method for Down's syndrome in women of AMA. PMID:27313855
Shitzer, Avraham; Arens, Edward; Zhang, Hui
The assignments of basal metabolic rates (BMR), basal cardiac output (BCO), and basal blood perfusion rates (BBPR) were compared in nine multi-compartment, whole-body thermoregulation models. The data are presented at three levels of detail: total body, specific body regions, and regional body tissue layers. Differences in the assignment of these quantities among the compared models increased with the level of detail, in the above order. The ranges of variability in the total body BMR was 6.5 % relative to the lowest value, with a mean of 84.3 ± 2 W, and in the BCO, it was 8 % with a mean of 4.70 ± 0.13 l/min. The least variability among the body regions is seen in the combined torso (shoulders, thorax, and abdomen: ±7.8 % BMR and ±5.9 % BBPR) and in the combined head (head, face, and neck ±9.9 % BMR and ±10.9 % BBPR), determined by the ratio of the standard deviation to the mean. Much more variability is apparent in the extremities with the most showing in the BMR of the feet (±117 %), followed by the BBPR in the arms (±61.3 %). In the tissue layers, most of the bone layers were assigned zero BMR and BBPR, except in the shoulders and in the extremities that were assigned non-zero values in a number of models. The next lowest values were assigned to the fat layers, with occasional zero values. Skin basal values were invariably non-zero but involved very low values in certain models, e.g., BBPR in the feet and the hands. Muscle layers were invariably assigned high values with the highest found in the thorax, abdomen, and legs. The brain, lung, and viscera layers were assigned the highest of all values of both basal quantities with those of the brain layers showing rather tight ranges of variability in both basal quantities. Average basal values of the "time-seasoned" models presented in this study could be useful as a first step in future modeling efforts subject to appropriate adjustment of values to conform to most recently available and reliable data.
Iwata, Sachiko; Tachtsidis, Ilias; Takashima, Sachio; Matsuishi, Toyojiro; Robertson, Nicola J; Iwata, Osuke
Small shifts in brain temperature after hypoxia-ischaemia affect cell viability. The main determinants of brain temperature are cerebral metabolism, which contributes to local heat production, and brain perfusion, which removes heat. However, few studies have addressed the effect of cerebral metabolism and perfusion on regional brain temperature in human neonates because of the lack of non-invasive cot-side monitors. This study aimed (i) to determine non-invasive monitoring tools of cerebral metabolism and perfusion by combining near-infrared spectroscopy and echocardiography, and (ii) to investigate the dependence of brain temperature on cerebral metabolism and perfusion in unsedated newborn infants. Thirty-two healthy newborn infants were recruited. They were studied with cerebral near-infrared spectroscopy, echocardiography, and a zero-heat flux tissue thermometer. A surrogate of cerebral blood flow (CBF) was measured using superior vena cava flow adjusted for cerebral volume (rSVC flow). The tissue oxygenation index, fractional oxygen extraction (FOE), and the cerebral metabolic rate of oxygen relative to rSVC flow (CMRO₂ index) were also estimated. A greater rSVC flow was positively associated with higher brain temperatures, particularly for superficial structures. The CMRO₂ index and rSVC flow were positively coupled. However, brain temperature was independent of FOE and the CMRO₂ index. A cooler ambient temperature was associated with a greater temperature gradient between the scalp surface and the body core. Cerebral oxygen metabolism and perfusion were monitored in newborn infants without using tracers. In these healthy newborn infants, cerebral perfusion and ambient temperature were significant independent variables of brain temperature. CBF has primarily been associated with heat removal from the brain. However, our results suggest that CBF is likely to deliver heat specifically to the superficial brain. Further studies are required to assess the
Sinjab, Khaled; Chung, Ming-Pang; Chiang, Yi-Chen; Wang, Hom-Lay; Giannobile, William V.; Kripfgans, Oliver D.
Purpose Facial crestal bone level and dimension determine function and esthetics of dentition and dental implants. We have previously demonstrated that ultrasound can identify bony and soft tissue structures in the oral cavity. The aim of this study is to evaluate the accuracy of using ultrasound to measure facial crestal bone level and thickness. Materials and methods A commercially available medical ultrasound scanner, paired with a 14 MHz imaging probe was used to scan dental and periodontal tissues at the mid-facial site of each tooth on 6 fresh cadavers. The alveolar crest level in relation to the cemento-enamel junction and its thickness on ultrasound images were measured and compared to those on cone-beam computed tomography (CBCT) scans and/or direct measurements on a total of 144 teeth. Results The mean crestal bone level measured by means of ultrasound, CBCT and direct measures was 2.66 ± 0.86 mm, 2.51 ± 0.82 mm, and 2.71 ± 1.04 mm, respectively. The mean crestal bone thickness was 0.71 ± 0.44 mm and 0.74 ± 0.34 mm, measured by means of ultrasound and CBCT, respectively. The correlations of the ultrasound readings to the other two methods were between 0.78 and 0.88. The mean absolute differences in crestal bone height and thickness between ultrasound and CBCT were 0.09 mm (-1.20 to 1.00 mm, p = 0.06) and 0.03 mm (-0.48 to 0.54 mm, p = 0.03), respectively. Conclusion Ultrasound was as accurate in determining alveolar bone level and its thickness as CBCT and direct measurements. Clinical trials will be required to further validate this non-ionizing and non-invasive method for determining facial crestal bone position and dimension. PMID:28178323
Shih, Ludy C.; Pascual-Leone, Alvaro
Background There is increasing interest in the use of non-invasive brain stimulation to characterize and potentially treat essential tremor (ET). Studies have used a variety of stimulation coils, paradigms, and target locations to make these observations. We reviewed the literature to compare prior studies and to evaluate the rationale and the methods used in these studies. Methods We performed a systematic literature search of the PubMed database using the terms “transcranial,” “noninvasive,” “brain stimulation,” “transcranial magnetic stimulation (TMS),” “transcranial direct current stimulation (tDCS),” “transcranial alternating current stimulation (tACS),” and “essential tremor.” Results Single pulses of TMS to the primary motor cortex have long been known to reset tremor. Although there are relatively few studies showing alterations in motor cortical physiology, such as motor threshold, short and long intracortical inhibition, and cortical silent period, there may be some evidence of altered intracortical facilitation and cerebello-brain inhibition in ET. Repetitive TMS, theta burst stimulation, tDCS, and tACS have been applied to human subjects with tremor with some preliminary signs of tremor reduction, particularly in those studies that employed consecutive daily sessions. Discussion A variety of stimulation paradigms and targets have been explored, with the increasing rationale an interest in targeting the cerebellum. Rigorous assessment of coil geometry, stimulation paradigm, rationale for selection of the specific anatomic target, and careful phenotypic and physiologic characterization of the subjects with ET undergoing these interventions may be critical in extending these preliminary findings into effective stimulation therapies. PMID:28373927
Masclans, J R; Pérez, M; Almirall, J; Lorente, L; Marqués, A; Socias, L; Vidaur, L; Rello, J
The role of non-invasive ventilation (NIV) in acute respiratory failure caused by viral pneumonia remains controversial. Our objective was to evaluate the use of NIV in a cohort of (H1N1)v pneumonia. Usefulness and success of NIV were assessed in a prospective, observational registry of patients with influenza A (H1N1) virus pneumonia in 148 Spanish intensive care units (ICUs) in 2009-10. Significant variables for NIV success were included in a multivariate analysis. In all, 685 patients with confirmed influenza A (H1N1)v viral pneumonia were admitted to participating ICUs; 489 were ventilated, 177 with NIV. The NIV was successful in 72 patients (40.7%), the rest required intubation. Low Acute Physiology and Chronic Health Evaluation (APACHE) II, low Sequential Organ Failure Assessment (SOFA) and absence of renal failure were associated with NIV success. Success of NIV was independently associated with fewer than two chest X-ray quadrant opacities (OR 3.5) and no vasopressor requirement (OR 8.1). However, among patients with two or more quadrant opacities, a SOFA score ≤7 presented a higher success rate than those with SOFA score >7 (OR 10.7). Patients in whom NIV was successful required shorter ventilation time, shorter ICU stay and hospital stay than NIV failure. In patients in whom NIV failed, the delay in intubation did not increase mortality (26.5% versus 24.2%). Clinicians used NIV in 25.8% of influenza A (H1N1)v viral pneumonia admitted to ICU, and treatment was effective in 40.6% of them. NIV success was associated with shorter hospital stay and mortality similar to non-ventilated patients. NIV failure was associated with a mortality similar to those who were intubated from the start.
Crosara, Stefano; D'Onofrio, Mirko; De Robertis, Riccardo; Demozzi, Emanuele; Canestrini, Stefano; Zamboni, Giulia; Pozzi Mucelli, Roberto
Autoimmune pancreatitis (AIP) is characterized by obstructive jaundice, a dramatic clinical response to steroids and pathologically by a lymphoplasmacytic infiltrate, with or without a pancreatic mass. Type 1 AIP is the pancreatic manifestation of an IgG4-related systemic disease and is characterized by elevated IgG4 serum levels, infiltration of IgG4-positive plasma cells and extrapancreatic lesions. Type 2 AIP usually has none or very few IgG4-positive plasma cells, no serum IgG4 elevation and appears to be a pancreas-specific disorder without extrapancreatic involvement. AIP is diagnosed in approximately 2%-6% of patients that undergo pancreatic resection for suspected pancreatic cancer. There are three patterns of autoimmune pancreatitis: diffuse disease is the most common type, with a diffuse, “sausage-like” pancreatic enlargement with sharp margins and loss of the lobular contours; focal disease is less common and manifests as a focal mass, often within the pancreatic head, mimicking a pancreatic malignancy. Multifocal involvement can also occur. In this paper we describe the features of AIP at ultrasonography, computed tomography, magnetic resonance and positron emission tomography/computed tomography imaging, focusing on diagnosis and differential diagnosis with pancreatic ductal adenocarcinoma. It is of utmost importance to make an early correct differential diagnosis between these two diseases in order to identify the optimal therapeutic strategy and to avoid unnecessary laparotomy or pancreatic resection in AIP patients. Non-invasive imaging plays also an important role in therapy monitoring, in follow-up and in early identification of disease recurrence. PMID:25493001
Rano, A; Agusti, C; Jimenez, P; Angrill, J; Benito, N; Danes, C; Gonzalez, J; Rovira, M; Pumarola, T; Moreno, A; Torres, A
BACKGROUND—The development of pulmonary infiltrates is a frequent life threatening complication in immunocompromised patients, requiring early diagnosis and specific treatment. In the present study non-invasive and bronchoscopic diagnostic techniques were applied in patients with different non-HIV immunocompromised conditions to determine the aetiology of the pulmonary infiltrates and to evaluate the impact of these methods on therapeutic decisions and outcome in this population. METHODS—The non-invasive diagnostic methods included serological tests, blood antigen detection, and blood, nasopharyngeal wash (NPW), sputum and tracheobronchial aspirate (TBAS) cultures. Bronchoscopic techniques included fibrobronchial aspirate (FBAS), protected specimen brush (PSB), and bronchoalveolar lavage (BAL). Two hundred consecutive episodes of pulmonary infiltrates were prospectively evaluated during a 30 month period in 52 solid organ transplant recipients, 53 haematopoietic stem cell transplant (HSCT) recipients, 68 patients with haematological malignancies, and 27 patients requiring chronic treatment with corticosteroids and/or immunosuppressive drugs. RESULTS—An aetiological diagnosis was obtained in 162 (81%) of the 200 patients. The aetiology of the pulmonary infiltrates was infectious in 125 (77%) and non-infectious in 37 (23%); 38 (19%) remained undiagnosed. The main infectious aetiologies were bacterial (48/125, 24%), fungal (33/125, 17%), and viral (20/125, 10%), and the most frequent pathogens were Aspergillus fumigatus (n=29), Staphylococcus aureus (n=17), and Pseudomonas aeruginosa (n=12). Among the non-infectious aetiologies, pulmonary oedema (16/37, 43%) and diffuse alveolar haemorrhage (10/37, 27%) were the most common causes. Non-invasive techniques led to the diagnosis of pulmonary infiltrates in 41% of the cases in which they were used; specifically, the diagnostic yield of blood cultures was 30/191 (16%); sputum cultures 27/88 (31%); NPW 9/50 (18
Park, Myoung-Hwan; Castleberry, Steven; Deng, Jason Z.; Hsu, Bryan; Mayner, Sarah; Jensen, Anne E.; Sequist, Lecia V.; Maheswaran, Shyamala; Haber, Daniel A.; Toner, Mehmet; Stott, Shannon L.; Hammond, Paula T.
Selective isolation and purification of circulating tumor cells (CTCs) from whole blood is an important capability for both clinical medicine and biological research. Current techniques to perform this task place the isolated cells under excessive stresses that reduce cell viability, and potentially induce phenotype change, therefore losing valuable information about the isolated cells. We present a biodegradable nano-film coating on the surface of a microfluidic chip, which can be used to effectively capture as well as non-invasively release cancer cell lines such as PC-3, LNCaP, DU 145, H1650 and H1975. We have applied layer-by-layer (LbL) assembly to create a library of ultrathin coatings using a broad range of materials through complementary interactions. By developing an LbL nano-film coating with an affinity-based cell-capture surface that is capable of selectively isolating cancer cells from whole blood, and that can be rapidly degraded on command, we are able to gently isolate cancer cells and recover them without compromising cell viability or proliferative potential. Our approach has the capability to overcome practical hurdles and provide viable cancer cells for downstream analyses, such as live cell imaging, single cell genomics, and in vitro cell culture of recovered cells. Furthermore, CTCs from cancer patients were also captured, identified, and successfully released using the LbL-modified microchips. PMID:26142780
Suwa, Kiyotaka; Momoi, Mariko Y
The diagnosis of fragile X A syndrome (FRAXA) during childhood depends largely on DNA-based diagnostic tests due to the lack of the specific clinical features. To determine a non-invasive screening method for fragile X syndrome, we studied the method of DNA-based diagnosis using urine or hair roots instead of routinely used peripheral blood cells. The amplification of repeat-containing alleles of FMR-1 by PCR using Pfu polymerase was applied on DNA extracted from urine sediments or hair roots of 50 and 28 normal individuals, respectively. Consistent amplification of repeat-containing DNA fragments of normal size to ethidium-visible quantities were obtained in 92% (46/50) of urine samples and 100% (28/28) of hair roots. No bands of normal size or abnormal or artificial smears were detected in two male FRAXA patients. No female samples were examined in the present study because the separation of two alleles was unsatisfactory on agarose gels with DNA from blood samples. Our results indicate that the use of hair roots in a DNA-based test constitutes a rapid, simple and less-invasive screen to diagnose males with FRAXA.
Wang, Chuan; Chen, Ying-Ge; Gao, Jian-Li; Lyu, Gui-Yuan; Su, Jie; Zhang, Q I; Ji, Xin; Yan, Ji-Zhong; Qiu, Qiao-Li; Zhang, Yue-Li; Li, Lin-Zi; Xu, Han-Ting; Chen, Su-Hong
It was originally thought that no single routine blood test result would be able to indicate whether or not a patient had cancer; however, several novel studies have indicated that the median survival and prognosis of cancer patients were markedly associated with the systemic circulation features of cancer patients. In addition, certain parameters, such as white blood cell (WBC) count, were largely altered in malignant tumors. In the present study, routine blood tests were performed in order to observe the change of blood cells in tumor-bearing mice following the implantation of 4T1 breast cancer cells into the mammary fat pad; in addition, blood flow in breast tumor sites was measured indirectly using laser Doppler perfusion imaging (LDPI), in an attempt to explain the relevance between the blood circulation features and the growth or metastasis of breast cancer in mice model. The LDPI and blood test results indicated that the implantation of 4T1 breast cancer cells into BALB/c mice led to thrombosis as well as high WBC count, high platelet count, high plateletcrit and low blood perfusion. Following implantation of the 4T1 cells for four weeks, the lung metastatic number was determined and the Pearson correlation coefficient revealed that the number of visceral lung metastatic sites had a marked negative association with the ratio of basophils (BASO%; r=-0.512; P<0.01) and the mean corpuscular hemoglobin was significantly correlated with primary tumor weight (r=0.425; P<0.05). In conclusion, the results of the present study demonstrated that tumor growth led to thrombosis and acute anemia in mice; in addition, when blood BASO% was low, an increased number of lung metastases were observed in tumor-bearing mice.
Yalcin, Ozlem; Ulker, Pinar; Yavuzer, Ugur; Meiselman, Herbert J; Baskurt, Oguz K
Endothelial function is modulated by wall shear stress acting on the vessel wall, which is determined by fluid velocity and the local viscosity near the vessel wall. Red blood cell (RBC) aggregation may affect the local viscosity by favoring axial migration. The aim of this study was to investigate the role of RBC aggregation, with or without altered plasma viscosity, in the mechanically induced nitric oxide (NO)-related mechanisms of endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultured on the inner surface of cylindrical glass capillaries that were perfused with RBC suspensions having normal and increased aggregation at a nominal shear stress of 15 dyn/cm(2). RBC aggregation was enhanced by two different approaches: 1) poloxamer-coated RBC suspended in normal, autologous plasma, resulting in enhanced aggregation but unchanged plasma viscosity and 2) normal RBC suspended in autologous plasma containing 0.5% dextran (mol mass 500 kDa), with a similar level of RBC aggregation but higher plasma viscosity. Compared with normal cells in unmodified plasma, perfusion with suspensions of poloxamer-coated RBC in normal plasma resulted in decreased levels of NO metabolites and serine 1177 phosphorylation of endothelial nitric oxide synthase (eNOS). Perfusion with normal RBC in plasma containing dextran resulted in a NO level that remained elevated, whereas only a modest decrease of phosphorylated eNOS level was observed. The results of this study suggest that increases of RBC aggregation tendency affect endothelial cell functions by altering local blood composition, especially if the alterations of RBC aggregation are due to modified cellular properties and not to plasma composition changes.
Tanaka, Rie; Sanada, Shigeru; Fujimura, Masaki; Yasui, Masahide; Hayashi, Norio; Tsuji, Shiro; Okamoto, Hiroyuki; Nanbu, Yuko; Matsui, Osamu
Pulmonary blood flow is reflected in dynamic chest radiographs as changes in X-ray translucency, i.e., pixel values. Thus, decreased blood flow should be observed as a reduction of the variation of X-ray translucency. We performed the present study to investigate the feasibility of pulmonary blood flow evaluation with a dynamic flat-panel detector (FPD). Sequential chest radiographs of 14 subjects were obtained with a dynamic FPD system. The changes in pixel value in each local area were measured and mapped on the original image by use of a gray scale in which small and large changes were shown in white and black, respectively. The resulting images were compared to the findings in perfusion scans. The cross-correlation coefficients of the changes in pixel value and radioactivity counts in each local area were also computed. In all patients, pulmonary blood flow disorder was indicated as a reduction of changes in pixel values on the mapping image, and a correlation was observed between the distribution of changes in pixel value and those in radioactivity counts (0.7
Cardiac Magnetic Resonance Myocardial Perfusion Reserve Index Is Reduced in Women With Coronary Microvascular Dysfunction: A National Heart, Lung and Blood Institute-Sponsored Study From the Women's Ischemia Syndrome Evaluation (WISE)
Thomson, Louise E.J.; Wei, Janet; Agarwal, Megha; Haft-Baradaran, Afsaneh; Shufelt, Chrisandra; Mehta, Puja K.; Gill, Edward; Johnson, B. Delia; Kenkre, Tanya; Handberg, Eileen; Li, Debiao; Sharif, Behzad; Berman, Daniel S.; Petersen, John; Pepine, Carl J.; Bairey Merz, C. Noel
Background Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD), diagnosed by invasive coronary reactivity testing (CRT). While traditional noninvasive stress imaging is often normal in CMD, cardiac magnetic resonance imaging (CMRI) may be able to detect CMD in this population. Methods and Results Vasodilator stress CMRI was performed in 118 women with suspected CMD who had undergone CRT and 21 asymptomatic reference subjects. Semi quantitative evaluation of the first-pass perfusion images was completed to determine myocardial perfusion reserve index (MPRI). The relationship between CRT findings and MPRI was examined by Pearson correlations, logistic regression and sensitivity/specificity. Symptomatic women had lower mean pharmacologic stress MPRI compared to reference subjects (1.71±0.43 vs. 2.23±0.37, p<0.0001). Lower MPRI was predictive of one or more abnormal CRT variables (OR = 0.78 [0.70, 0.88], p<0.0001, c-statistic 0.78 [0.68, 0.88]). An MPRI threshold of 1.84 predicted CRT abnormality with sensitivity 73% and specificity 74%. Conclusions Noninvasive CMRI MPRI can detect CMD defined by invasive CRT. Further work is aimed to optimize the non-invasive identification and management of CMD patients. PMID:25801710
Abadesso, Clara; Nunes, Pedro; Silvestre, Catarina; Matias, Ester; Loureiro, Helena; Almeida, Helena
The aim of this paper is to assess the clinical efficacy of non-invasive ventilation (NIV) in avoiding endotracheal intubation (ETI), to demonstrate clinical and gasometric improvement and to identify predictive risk factors associated with NIV failure. An observational prospective clinical study was carried out. Included Patients with acute respiratory disease (ARD) treated with NIV, from November 2006 to January 2010 in a Pediatric Intensive Care Unit (PICU). NIV was used in 151 patients with acute respiratory failure (ARF). Patients were divided in two groups: NIV success and NIV failure, if ETI was required. Mean age was 7.2±20.3 months (median: 1 min: 0,3 max.: 156). Main diagnoses were bronchiolitis in 102 (67.5%), and pneumonia in 44 (29%) patients. There was a significant improvement in respiratory rate (RR), heart rate (HR), pH, and pCO2 at 2, 6, 12 and 24 hours after NIV onset (P<0.05) in both groups. Improvement in pulse oximetric saturation/fraction of inspired oxygen (SpO2/FiO2) was verified at 2, 4, 6, 12 and 24 hours after NIV onset in the success group (P<0.001). In the failure group, significant SpO2/FiO2 improvement was only observed in the first 4 hours. NIV failure occurred in 34 patients (22.5%). Risk factors for NIV failure were apnea, prematurity, pneumonia, and bacterial co-infection (P<0.05). Independent risk factors for NIV failure were apneia (P<0.001; odds ratio 15.8; 95% confidence interval: 3.42–71.4) and pneumonia (P<0.001, odds ratio 31.25; 95% confidence interval: 8.33–111.11). There were no major complications related with NIV. In conclusion this study demonstrates the efficacy of NIV as a form of respiratory support for children and infants with ARF, preventing clinical deterioration and avoiding ETI in most of the patients. Risk factors for failure were related with immaturity and severe infection. PMID:22802994
Clarke, Jon V; Riches, Philip E; Picard, Frederic; Deakin, Angela H
The quantification of knee alignment is a routine part of orthopaedic practice and is important for monitoring disease progression, planning interventional strategies, and follow-up of patients. Currently available technologies such as radiographic measurements have a number of drawbacks. The aim of this study was to validate a potentially improved technique for measuring knee alignment under different conditions. An image-free navigation system was adapted for non-invasive use through the development of external infrared tracker mountings. Stability was assessed by comparing the variance (F-test) of repeated mechanical femoro-tibial (MFT) angle measurements for a volunteer and a leg model. MFT angles were then measured supine, standing and with varus-valgus stress in asymptomatic volunteers who each underwent two separate registrations and repeated measurements for each condition. The mean difference and 95% limits of agreement were used to assess intra-registration and inter-registration repeatability. For multiple registrations the range of measurements for the external mountings was 1° larger than for the rigid model with statistically similar variance (p=0.34). Thirty volunteers were assessed (19 males, 11 females) with a mean age of 41 years (range: 20-65) and a mean BMI of 26 (range: 19-34). For intra-registration repeatability, consecutive coronal alignment readings agreed to almost ±1°, with up to ±0.5° loss of repeatability for coronal alignment measured before and after stress maneuvers, and a ±0.2° loss following stance trials. Sagittal alignment measurements were less repeatable overall by an approximate factor of two. Inter-registration agreement limits for coronal and sagittal supine MFT angles were ±1.6° and ±2.3°, respectively. Varus and valgus stress measurements agreed to within ±1.3° and ±1.1°, respectively. Agreement limits for standing MFT angles were ±2.9° (coronal) and ±5.0° (sagittal), which may have reflected a variation
Hennig, Georg; Homann, Christian; Teksan, Ilknur; Hasbargen, Uwe; Hasmüller, Stephan; Holdt, Lesca M.; Khaled, Nadia; Sroka, Ronald; Stauch, Thomas; Stepp, Herbert; Vogeser, Michael; Brittenham, Gary M.
Worldwide, more individuals have iron deficiency than any other health problem. Most of those affected are unaware of their lack of iron, in part because detection of iron deficiency has required a blood sample. Here we report a non-invasive method to optically measure an established indicator of iron status, red blood cell zinc protoporphyrin, in the microcirculation of the lower lip. An optical fibre probe is used to illuminate the lip and acquire fluorescence emission spectra in ∼1 min. Dual-wavelength excitation with spectral fitting is used to distinguish the faint zinc protoporphyrin fluorescence from the much greater tissue background fluorescence, providing immediate results. In 56 women, 35 of whom were iron-deficient, the sensitivity and specificity of optical non-invasive detection of iron deficiency were 97% and 90%, respectively. This fluorescence method potentially provides a rapid, easy to use means for point-of-care screening for iron deficiency in resource-limited settings lacking laboratory infrastructure. PMID:26883939
Hardman, Ron C; Kullman, Seth W; Hinton, David E
Background A novel transparent stock of medaka (Oryzias latipes; STII), recessive for all pigments found in chromatophores, permits transcutaneous imaging of internal organs and tissues in living individuals. Findings presented describe the development of methodologies for non invasive in vivo investigation in STII medaka, and the successful application of these methodologies to in vivo study of hepatobiliary structure, function, and xenobiotic response, in both 2 and 3 dimensions. Results Using brightfield, and widefield and confocal fluorescence microscopy, coupled with the in vivo application of fluorescent probes, structural and functional features of the hepatobiliary system, and xenobiotic induced toxicity, were imaged at the cellular level, with high resolution (< 1 μm), in living individuals. The findings presented demonstrate; (1) phenotypic response to xenobiotic exposure can be investigated/imaged in vivo with high resolution (< 1 μm), (2) hepatobiliary transport of solutes from blood to bile can be qualitatively and quantitatively studied/imaged in vivo, (3) hepatobiliary architecture in this lower vertebrate liver can be studied in 3 dimensions, and (4) non invasive in vivo imaging/description of hepatobiliary development in this model can be investigated. Conclusion The non-invasive in vivo methodologies described are a unique means by which to investigate biological structure, function and xenobiotic response with high resolution in STII medaka. In vivo methodologies also provide the future opportunity to integrate molecular mechanisms (e.g., genomic, proteomic) of disease and toxicity with phenotypic changes at the cellular and system levels of biological organization. While our focus has been the hepatobiliary system, other organ systems are equally amenable to in vivo study, and we consider the potential for discovery, within the context of in vivo investigation in STII medaka, as significant. PMID:18838008
Hogan, Harry A.; Webster, Laurie
An important component in developing countermeasures for maintaining musculoskeletal integrity during long-term space flight is an effective and meaningful method of monitoring skeletal condition. Magnetic resonance imaging (MRI) is an attractive non-invasive approach because it avoids the exposure to radiation associated with X-ray based imaging and also provides measures related to bone microstructure rather than just density. The purpose of the research for the 1996 Summer Faculty Fellowship period was to extend the usefulness of the MRI data to estimate the mechanical properties of trabecular bone. The main mechanical properties of interest are the elastic modulus and ultimate strength. Correlations are being investigated between these and fractal analysis parameters, MRI relaxation times, apparent densities, and bone mineral densities. Bone specimens from both human and equine donors have been studied initially to ensure high-quality MR images. Specimens were prepared and scanned from human proximal tibia bones as well as the equine distal radius. The quality of the images from the human bone appeared compromised due to freezing artifact, so only equine bone was included in subsequent procedures since these specimens could be acquired and imaged fresh before being frozen. MRI scans were made spanning a 3.6 cm length on each of 5 equine distal radius specimens. The images were then sent to Dr. Raj Acharya of the State University of New York at Buffalo for fractal analysis. Each piece was cut into 3 slabs approximately 1.2 cm thick and high-resolution contact radiographs were made to provide images for comparing fractal analysis with MR images. Dual energy X-ray absorptiometry (DEXA) scans were also made of each slab for subsequent bone mineral density determination. Slabs were cut into cubes for mechanical using a slow-speed diamond blade wafering saw (Buehler Isomet). The dimensions and wet weights of each cube specimen were measured and recorded. Wet weights
Toronov, V.; Myllylä, T.; Kiviniemi, V.; Tuchin, V. V.
Dynamics is an essential aspect of the brain function. In this article we review theoretical models of neural and haemodynamic processes in the human brain and experimental non-invasive techniques developed to study brain functions and to measure dynamic characteristics, such as neurodynamics, neurovascular coupling, haemodynamic changes due to brain activity and autoregulation, and cerebral metabolic rate of oxygen. We focus on emerging theoretical biophysical models and experimental functional neuroimaging results, obtained mostly by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS). We also included our current results on the effects of blood pressure variations on cerebral haemodynamics and simultaneous measurements of fast processes in the brain by near-infrared spectroscopy and a very novel functional MRI technique called magnetic resonance encephalography. Based on a rapid progress in theoretical and experimental techniques and due to the growing computational capacities and combined use of rapidly improving and emerging neuroimaging techniques we anticipate during next decade great achievements in the overall knowledge of the human brain.
Rogers, Lesco L.; Ade, Kristen K.; Nicoletto, Heather A.; Adkins, Heather D.; Laskowitz, Daniel T.
Caloric vestibular stimulation (CVS) to elicit the vestibulo-ocular reflex has long been used in clinical settings to aid in the diagnosis of balance disorders and to confirm the absence of brainstem function. While a number of studies have hinted at the potential therapeutic applications of CVS, the limitations of existing devices have frustrated that potential. Current CVS irrigators use water or air during short-duration applications; however, this approach is not tenable for longer duration therapeutic protocols or home use. Here, we describe a solid-state CVS device we developed in order to address these limitations. This device delivers tightly controlled time-varying thermal waveforms, which can be programmed through an external control unit. It contains several safety features, which limit patients to the prescribed waveform and prevent the potential for temperature extremes. In this paper, we provide evidence that CVS treatment with time-varying, but not constant temperature waveforms, elicits changes in cerebral blood flow physiology consistent with the neuromodulation of brainstem centers, and we present results from a small pilot study, which demonstrate that the CVS can safely and feasibly be used longitudinally in the home setting to treat episodic migraine. Together, these results indicate that this solid-state CVS device may be a viable tool for non-invasive neuromodulation. PMID:27777829
Oshinsky, Michael L.; Murphy, Angela L.; Hekierski, Hugh; Cooper, Marnie; Simon, Bruce J.
Implanted vagus nerve stimulation (VNS) has been used to treat seizures and depression. In this study, we explore the mechanism of action of non-invasive vagus nerve stimulation (nVNS) for the treatment of trigeminal allodynia. Rats were repeatedly infused with inflammatory mediators directly onto the dura, which leads to chronic trigeminal allodynia. nVNS for 2min decreases periorbital sensitivity in rats with periorbital trigeminal allodynia for up to 3.5hr after stimulation. Using microdialysis, we quantified levels of extracellular neurotransmitters in the trigeminal nucleus caudalis (TNC). Allodynic rats showed a 7.7±0.9 fold increase in extracellular glutamate in the TNC following i.p. administration of the chemical headache trigger, glyceryl trinitrate (GTN; 0.1mg/kg). Allodynic rats, which received nVNS, had only a 2.3±0.4 fold increase in extracellular glutamate following GTN similar to the response in control naive rats. When nVNS was delayed until 120min after GTN treatment, the high levels of glutamate in the TNC were reversed following nVNS. The nVNS stimulation parameters used in this study did not produce significant changes in blood pressure or heart rate. These data suggest that nVNS may be used to treat trigeminal allodynia. PMID:24530613
Yan, Zhang; Xin, Liu; Scopesi, Fabio; Serra, Giovanni; Sun, Jinwei; Rolfe, Peter
A diverse range of sensors and instruments is available for use in the critical care of acutely ill patients and it is not always straightforward to decide which technologies should be used. Clinicians have their own priorities for the physiological variables that they consider need to be monitored in order to provide optimum medical care. Alongside this, consideration must be given to the choice of available technologies. This choice may be influenced by performance criteria, cost, and ease of use. It is also necessary to consider the physical status of the patients, the measurement instruments and any potential risks for the patients so as to provide the best measurement scheme. This paper explores the use of decision support tools that may be used in critical care situations. The care of ill newborn babies requiring mechanical ventilation is considered as a case study. The choice of invasive and non-invasive techniques for blood gas and pH assessment is evaluated and decision trees and hierarchical clustering are considered as possible decision support methodologies.
Hall, Alison; Bostanci, A; Wright, C F
Cell-free fetal DNA and RNA circulating in maternal blood can be used for the early non-invasive prenatal diagnosis (NIPD) of an increasing number of genetic conditions, both for pregnancy management and to aid reproductive decision-making. Here we present a brief review of the scientific and clinical status of the technology, and an overview of key ethical, legal and social issues raised by the analysis of cell-free fetal DNA for NIPD. We suggest that the less invasive nature of the technology brings some distinctive issues into focus, such as the possibility of broader uptake of prenatal diagnosis and access to the technology directly by the consumer via the internet, which have not been emphasised in previous work in this area. We also revisit significant issues that are familiar from previous debates about prenatal testing. Since the technology seems to transect existing distinctions between screening and diagnostic tests, there are important implications for the form and process involved in obtaining informed consent or choice. This analysis forms part of the work undertaken by a multidisciplinary group of experts which made recommendations about the implementation of this technology within the UK National Health Service.
Rehberger, Matthias; Giovannella, Martina; Pagliazzi, Marco; Weigel, Udo; Durduran, Turgut; Contini, Davide; Spinelli, Lorenzo; Pifferi, Antonio; Torricelli, Alessandro; Schmitt, Robert
Improved cerebral monitoring systems are needed to prevent preterm infants from long-term cognitive and motor restrictions. Combining advanced near-infrared diffuse spectroscopy measurement technologies, time-resolved spectroscopy (TRS) and diffuse correlation spectroscopy (DCS) will introduce novel indicators of cerebral oxygen metabolism and blood flow for neonatology. For non-invasive sensing a fiber-optical probe is used to send and receive light from the infant head. In this study we introduce a new fiber-based hybrid probe that is designed for volume production. The probe supports TRS and DCS measurements in a cross geometry, thus both technologies gain information on the same region inside the tissue. The probe is highly miniaturized to perform cerebral measurements on heads of extreme preterm infants down to head diameters of 6cm. Considerations concerning probe production focus on a reproducible accuracy in shape and precise optical alignment. In this way deviations in measurement data within a series of probes should be minimized. In addition to that, requirements for clinical use like robustness and hygiene are considered. An additional soft-touching sleeve made of FDA compatible silicone allows for a flexible attachment with respect to the individual anatomy of each patient. We present the technical concept of the hybrid probe and corresponding manufacturing methods. A prototype of the probe is shown and tested on tissue phantoms as well as in vivo to verify its operational reliability.
Lam, Kwok Ho; Li, Ying; Li, Yang; Lim, Hae Gyun; Zhou, Qifa; Shung, Koping Kirk
Non-contact precise manipulation of single microparticles, cells, and organisms has attracted considerable interest in biophysics and biomedical engineering. Similar to optical tweezers, acoustic tweezers have been proposed to be capable of manipulating microparticles and even cells. Although there have been concerted efforts to develop tools for non-contact manipulation, no alternative to complex, unifunctional tweezer has yet been found. Here we report a simple, low-cost, multifunctional single beam acoustic tweezer (SBAT) that is capable of manipulating an individual micrometer scale non-spherical cell at Rayleigh regime and even a single millimeter scale organism at Mie regime, and imaging tissue as well. We experimentally demonstrate that the SBAT with an ultralow f-number (f# = focal length/aperture size) could manipulate an individual red blood cell and a single 1.6 mm-diameter fertilized Zebrafish egg, respectively. Besides, in vitro rat aorta images were collected successfully at dynamic foci in which the lumen and the outer surface of the aorta could be clearly seen. With the ultralow f-number, the SBAT offers the combination of large acoustic radiation force and narrow beam width, leading to strong trapping and high-resolution imaging capabilities. These attributes enable the feasibility of using a single acoustic device to perform non-invasive multi-functions simultaneously for biomedical and biophysical applications. PMID:27874052
Pinheiro, T.; Fleming, R.; Gonçalves, A.; Neres, M.; Alves, L. C.; Silva, J. N.; Filipe, P.; Silva, R.
Hemochromatosis is a hereditary disease that causes an inappropriate intestinal absorption of Fe resulting in its accumulation in multiple organs, such as liver, heart and skin. Fe metabolism indicators in the circulation do not provide reliable indication of organ overload as they can be influenced by other clinical conditions. Assessing metabolism organs such as liver requires invasive procedures which is not adequate to patient's serial observations. Our aim was establishing cross sectional and longitudinal information on the amount of Fe that deposited in skin and liver during a life period, how iron is cleared out by therapy intervention and study the relationship of these changes between the two organs using non-invasive methods. Results on skin Fe deposition were evaluated by nuclear microscopy techniques and liver Fe concentrations determined by quantitative magnetic resonance imaging. Skin and liver Fe concentrations were correlated. Though Fe deposits in the two organs were differently associated with blood Fe metabolism conventional markers. Fe serial variations in skin and liver highlighted the value of assessing Fe organ deposits for estimating hemochromatosis evolution and therapy efficacy.
Lam, Kwok Ho; Li, Ying; Li, Yang; Lim, Hae Gyun; Zhou, Qifa; Shung, Koping Kirk
Non-contact precise manipulation of single microparticles, cells, and organisms has attracted considerable interest in biophysics and biomedical engineering. Similar to optical tweezers, acoustic tweezers have been proposed to be capable of manipulating microparticles and even cells. Although there have been concerted efforts to develop tools for non-contact manipulation, no alternative to complex, unifunctional tweezer has yet been found. Here we report a simple, low-cost, multifunctional single beam acoustic tweezer (SBAT) that is capable of manipulating an individual micrometer scale non-spherical cell at Rayleigh regime and even a single millimeter scale organism at Mie regime, and imaging tissue as well. We experimentally demonstrate that the SBAT with an ultralow f-number (f# = focal length/aperture size) could manipulate an individual red blood cell and a single 1.6 mm-diameter fertilized Zebrafish egg, respectively. Besides, in vitro rat aorta images were collected successfully at dynamic foci in which the lumen and the outer surface of the aorta could be clearly seen. With the ultralow f-number, the SBAT offers the combination of large acoustic radiation force and narrow beam width, leading to strong trapping and high-resolution imaging capabilities. These attributes enable the feasibility of using a single acoustic device to perform non-invasive multi-functions simultaneously for biomedical and biophysical applications.
Zhao, Siwei; Tao, Wei; He, Qiaozhi; Zhao, Hui; Cao, Wenwu
Diabetes mellitus (DM) is a chronic disease affecting nearly 400 million people worldwide. In order to manage the disease, patients need to monitor the blood glucose level by puncturing the finger several times a day, which is uncomfortable and inconvenient. We present here a potential non-invasive monitoring method based on the velocity of ultrasonic waves generated in glucose solution by the photoacoustic principal, which can recognize the glucose concentration down to 20mg/dL. In order to apply this method to warm bodies, we carefully designed the experiment and performed measurements from 30 °C to 50 °C to generate a set of calibration curves, which may be used by engineers to build devices. Most importantly, we have theoretically explained the relationship between the compressibility and the glucose concentration. Our results show that the compressibility of solution decreases with the glucose concentration, which clarified the controversy between theory and experiment results in the literature. The derived formula is generally validity, which can be used to nondestructively measure solution concentration for other types of solutions using photoacoustic principle.
Antonaglia, Vittorio; Ferluga, Massimo; Capitanio, Guido; Lucangelo, Umberto; Piller, Fulvia; Roman-Pognuz, Erik; Biancardi, Bruno; Caggegi, Giuseppe Davide; Zin, Walter A
Non-invasive positive pressure ventilation (NPPV) is the first choice to treat exacerbations in COPD patients. NPPV can fail owing to different causes related to gas exchange impairment (RF group) or intolerance (INT group). To assess if the respiratory mechanical properties and the ratio between the dynamic and static intrinsic positive end-expiratory pressure (PEEP(i),dyn/PEEP(i),stat), reflecting lung mechanical inequalities, were different between groups, 29 COPD patients who failed NPPV (15 RF and 14 INT) were studied, early after the application of invasive ventilation. Blood gas analysis, clinical status, and mechanical properties were measured. pH was higher in INT patients before intubation (p<0.001). PEEP(i),dyn/PEEP(i),stat was found higher in INT group with (p=0.021) and without PEEP (ZEEP, p<0.01). PEEP(i),dyn/PEEP(i),stat was exponentially associated with the duration of NPPV in INT group (p=0.011). INT and RF patients had similar impairment of respiratory system resistance and elastance.
Feng, Xiao-Yuan; Qiang, Jin-Wei; Zhang, Jia-wen; Wang, Yong-gang; Liu, Ying
, proliferation marker and cerebral blood flow percentage changes, cerebral blood volume percentage changes. Conclusion Our findings suggest that CT perfusion with challenge can provide new insight into non-invasive assessment of rat C6 glioma angiogenesis. PMID:25781321
Ultrasonic Diagnosing and Monitoring of Intracranial Pressure/Volume PRINCIPAL INVESTIGATOR: Aloyzas Petrikas, Ph.D. Arminas Ragauskas Gediminas...Ultrasonic Diagnosing and Monitoring of DAMD17-00-2-0065 Intracranial Pressure/Volume 6. AUTHOR(S) Aloyzas Petrikas, Ph.D. Arminas Ragauskas Gediminas...Objectives were to verify the innovative concepts of non-invasive intracranial pressure (ICP) absolute value measurement and non- invasive
Yifat, Jonathan; Gannot, Israel
Early detection of malignant tumors plays a crucial role in the survivability chances of the patient. Therefore, new and innovative tumor detection methods are constantly searched for. Tumor-specific magnetic-core nano-particles can be used with an alternating magnetic field to detect and treat tumors by hyperthermia. For the analysis of the method effectiveness, the bio-heat transfer between the nanoparticles and the tissue must be carefully studied. Heat diffusion in biological tissue is usually analyzed using the Pennes Bio-Heat Equation, where blood perfusion plays an important role. Malignant tumors are known to initiate an angiogenesis process, where endothelial cell migration from neighboring vasculature eventually leads to the formation of a thick blood capillary network around them. This process allows the tumor to receive its extensive nutrition demands and evolve into a more progressive and potentially fatal tumor. In order to assess the effect of angiogenesis on the bio-heat transfer problem, we have developed a discrete stochastic 3D model & simulation of tumor-induced angiogenesis. The model elaborates other angiogenesis models by providing high resolution 3D stochastic simulation, capturing of fine angiogenesis morphological features, effects of dynamic sprout thickness functions, and stochastic parent vessel generator. We show that the angiogenesis realizations produced are well suited for numerical bio-heat transfer analysis. Statistical study on the angiogenesis characteristics was derived using Monte Carlo simulations. According to the statistical analysis, we provide analytical expression for the blood perfusion coefficient in the Pennes equation, as a function of several parameters. This updated form of the Pennes equation could be used for numerical and analytical analyses of the proposed detection and treatment method.
Kowalewski, K; Kolodej, A
Isolated, ex vivo perfused, canine stomachs were used for this study. Gastric secretion, myoelectrical activity and mechanical activity were recorded during stimulation of gastric function with pentagastrin or histamine alone or combined with calcium gluconate. Secretagogues and calcium were infused into the gastric arterial circulation. Hypercalcemia induced significant inhibition of pentagastrin, stimulated gastric secretion, but did not affect the secretion stimulated by histamine. Hypercalcemia also induced an increase of frequency of cycles of electrical control activity and a decrease of mechanical activity of the gastric antrum. The effect of hypercalcemia on gastric motor function was similar in the nonstimulated stomach and during the infusion of secretagogues used in this experiment.
Yost, William T. (Inventor); Cantrell, John H., Jr. (Inventor); Hargens, Alan E. (Inventor)
A method is presented for determining absolute intracranial pressure (ICP) in a patient. Skull expansion is monitored while changes in ICP are induced. The patient's blood pressure is measured when skull expansion is approximately zero. The measured blood pressure is indicative of a reference ICP value. Subsequently, the method causes a known change in ICP and measured the change in skull expansion associated therewith. The absolute ICP is a function of the reference ICP value, the known change in ICP and its associated change in skull expansion; and a measured change in skull expansion.
Page, Michael J.; Lourenço, André L.; David, Tovo; LeBeau, Aaron M.; Cattaruzza, Fiore; Castro, Helena C.; VanBrocklin, Henry F.; Coughlin, Shaun R.; Craik, Charles S.
Functional imaging of proteolytic activity is an emerging strategy to quantify disease and response to therapy at the molecular level. We present a new peptide-based imaging probe technology that advances these goals by exploiting enzymatic activity to deposit probes labelled with near-infrared (NIR) fluorophores or radioisotopes in cell membranes of disease-associated proteolysis. This strategy allows for non-invasive detection of protease activity in vivo and ex vivo by tracking deposited probes in tissues. We demonstrate non-invasive detection of thrombin generation in a murine model of pulmonary embolism using our protease-activated peptide probes in microscopic clots within the lungs with NIR fluorescence optical imaging and positron-emission tomography. Thrombin activity is imaged deep in tissue and tracked predominantly to platelets within the lumen of blood vessels. The modular design of our probes allows for facile investigation of other proteases, and their contributions to disease by tailoring the protease activation and cell-binding elements. PMID:26423607
Bastianini, Stefano; Alvente, Sara; Berteotti, Chiara; Lo Martire, Viviana; Silvani, Alessandro; Swoap, Steven J.; Valli, Alice; Zoccoli, Giovanna; Cohen, Gary
A major limitation in the study of sleep breathing disorders in mouse models of pathology is the need to combine whole-body plethysmography (WBP) to measure respiration with electroencephalography/electromyography (EEG/EMG) to discriminate wake-sleep states. However, murine wake-sleep states may be discriminated from breathing and body movements registered by the WBP signal alone. Our goal was to compare the EEG/EMG-based and the WBP-based scoring of wake-sleep states of mice, and provide formal guidelines for the latter. EEG, EMG, blood pressure and WBP signals were simultaneously recorded from 20 mice. Wake-sleep states were scored based either on EEG/EMG or on WBP signals and sleep-dependent respiratory and cardiovascular estimates were calculated. We found that the overall agreement between the 2 methods was 90%, with a high Cohen’s Kappa index (0.82). The inter-rater agreement between 2 experts and between 1 expert and 1 naïve sleep investigators gave similar results. Sleep-dependent respiratory and cardiovascular estimates did not depend on the scoring method. We show that non-invasive discrimination of the wake-sleep states of mice based on visual inspection of the WBP signal is accurate, reliable and reproducible. This work may set the stage for non-invasive high-throughput experiments evaluating sleep and breathing patterns on mouse models of pathophysiology. PMID:28139776
Fetita, Catalin; Thong, William E.; Ou, Phalla
This paper addresses the study of semi-quantitative assessment of pulmonary perfusion acquired from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a study population mainly composed of children with pulmonary malformations. The automatic analysis approach proposed is based on the indicator-dilution theory introduced in 1954. First, a robust method is developed to segment the pulmonary artery and the lungs from anatomical MRI data, exploiting 2D and 3D mathematical morphology operators. Second, the time-dependent contrast signal of the lung regions is deconvolved by the arterial input function for the assessment of the local hemodynamic system parameters, ie. mean transit time, pulmonary blood volume and pulmonary blood flow. The discrete deconvolution method implements here a truncated singular value decomposition (tSVD) method. Parametric images for the entire lungs are generated as additional elements for diagnosis and quantitative follow-up. The preliminary results attest the feasibility of perfusion quantification in pulmonary DCE-MRI and open an interesting alternative to scintigraphy for this type of evaluation, to be considered at least as a preliminary decision in the diagnostic due to the large availability of the technique and to the non-invasive aspects.
Zaouter, Cédrick; Zavorsky, Gerald S
The pulse CO-oximeter (Rad-57 Masimo Corporation, Irvine, CA) allows non-invasive and instantaneous measurement of carboxyhemoglobin (COHb) and methemoglobin (MetHb) percentage level using a finger probe. However, the accuracy and reliability of the Rad-57 against the gold standard of venous or arterial blood samples have not been clearly established. Thus, the objective of this trial is to evaluate the accuracy and precision of the Rad-57 pulse CO-oximeter by comparing it with venous sampling on the same subjects. Nine healthy subjects were subjected to carbon monoxide such that it raised the COHb to 10-14% on two different days and pooled together. The COHb and MetHb were measured with a blood gas-analyzer and simultaneously with the Rad-57 as the COHb increased from 1.4 to 14%. Results were compared using linear regression and a Bland and Altman method comparison. Mean bias and precision for COHb measured with the Rad-57 was -1% and 2.5%, respectively. The mean bias and precision for MetHb measured with the Rad-57 was 0.0% and 0.3%, respectively. The ability to detect a COHb ≥ 10% occurred in 54% of the samples in which COHb was ≥ 10-14%. In conclusion, the Rad-57 provides a reading that is between -6% and +4% of the true COHb value for 95% of all samples. The Rad-57 seems to be a good substitute as a first screening test of COHb when the pulse CO-oximeter reads <15%.
Serda, R; Savage, D; Corr, S; Curley, S
Purpose: The sad truth is that cancer is blamed for the death of nearly one in four people in the US. Immunotherapy offers hope for stimulating cancer immunity leading to targeted killing of cancer cells and a preventative measure for cancer recurrence. Unfortunately, the clinical efficacy of immunotherapy has not yet been established, however novel approaches are being developed, including combining immunotherapy with traditional chemotherapy, radiotherapy or thermal therapy. Therapeutics such as radiofrequency (RF) ablation and select chemotherapeutics induce mild anticancer immune responses. This project seeks to enhance the immune responses stimulated by these agents by co-delivery of nanoparticle-based chemotherapeutics and immune modulators in the presence of RF induced hyperthermia. Methods: A 4T1 mouse model of breast cancer is used to test the ability of RF waves to enhance accumulation of nanoparticles in tumor tissue by increasing blood flow and extravation of nanoparticles from hyperpermeable vessels. Images of particle and cell trafficking in the tumor are captured using an integrated RF and confocal imaging system, and tumor growth is monitored by tumor bioluminescence and caliper measurements. Results: Here we demonstrate enhanced intratumoral blood flow induced by non-invasive RF waves and an increase in nanoparticle accumulation in the tumor. IL-12 is shown to have powerful anti-tumor effects leading to tumor regression and the release of Th1-biased cytokines. Doxorubicin nanoparticles combined with adjuvant nanoparticles exhibited superior antitumor effects to single agent therapy. Conclusion: RF therapy combined with nanotherapeutics is a promising approach to enhance the delivery of therapeutics to the tumor and to stimulate a tumor microenvironment that supports the development of cancer-specific immune responses. This research was supported by the National Institute of Health grant numbers U54 CA143837 and U54 CA151668, and the Kanzius
Crespi, F.; Donini, M.; Bandera, A.; Congestri, F.; Formenti, F.; Sonntag, V.; Heidbreder, C.; Rovati, L.
The feasibility of non-invasive analysis of brain activities was studied in the attempt to overcome the major limitation of actual in vivo methodologies, i.e. invasiveness. Optic fibre probes were used as the optical head of a novel, highly sensitive near-infrared continuous wave spectroscopy (CW-NIR) instrument. This prototype was designed for non-invasive analysis of the two main forms of haemoglobin: oxy-haemoglobin (HbO2) and deoxy-haemoglobin (Hb), chromophores present in biological tissues. It was tested in peripheral tissue (human gastrocnemius muscle) and then reset to perform the measurement on rat brain. In animal studies, the optical head was firmly placed using stereotaxic apparatus upon the sagittal line of the head of anaesthetized adult rats, without any surgery. Then pharmacological treatments with saline (300 µl s.c.) amphetamine (2 mg kg-1) or nicotine (0.4 mg kg-1) were performed. Within 10-20 min amphetamine substantially increased HbO2 and reduced Hb control levels. Nicotine produced a rapid initial increase followed by a decrease in HbO2. In contrast to amphetamine, nicotine treatment also reduced Hb and blood volume. These results support the capacity of our CW-NIR prototype to measure non-invasively HbO2 and Hb levels in the rat brain, that are markers of the degree of tissue oxygenation, thus providing an index of blood levels and therefore of brain metabolism.
Shah, Brijesh; Khunt, Dignesh; Misra, Manju; Padh, Harish
Systemic drug delivery in schizophrenia is a major challenge due to presence of obstacles like, blood-brain barrier and P-glycoprotein, which prohibit entry of drugs into the brain. Quetiapine fumarate (QF), a substrate to P-glycoprotein under goes extensive first pass metabolism leading to limited absorption thus necessitating frequent oral administration. The aim of this study was to develop QF based microemulsion (ME) with and without chitosan (CH) to investigate its potential use in improving the bioavailability and brain targeting efficiency following non-invasive intranasal administration. QF loaded ME and mucoadhesive ME (MME) showed globule size, pH and viscosity in the range of 29-47nm, 5.5-6.5 and 17-40cP respectively. CH-ME with spherical globules having mean size of 35.31±1.71nm, pH value of 5.61±0.16 showed highest ex-vivo nasal diffusion (78.26±3.29%) in 8h with no sign of structural damage upon histopathological examination. Circular plume with an ovality ratio closer to 1.3 for CH-ME depicted ideal spray pattern. Significantly higher brain/blood ratio of CH-ME in comparison to QF-ME and drug solution following intranasal administration revealed prolonged retention of QF at site of action suggesting superiority of CH as permeability enhancer. Following intranasal administration, 2.7 and 3.8 folds higher nasal bioavailability in brain with CH-ME compared to QF-ME and drug solution respectively is indicative of preferential nose to brain transport (80.51±6.46%) bypassing blood-brain barrier. Overall, the above finding shows promising results in the area of developing non-invasive intranasal route as an alternative to oral route for brain delivery.
Huhndorf, Monika; Moussavi, Amir; Kramann, Nadine; Will, Olga; Hattermann, Kirsten; Stadelmann, Christine; Jansen, Olav
Objectives Angiogenesis and anti-angiogenetic medications play an important role in progression and therapy of glioblastoma. In this context, in vivo characterization of the blood-brain-barrier and tumor vascularization may be important for individual prognosis and therapy optimization. Methods We analyzed perfusion and capillary permeability of C6-gliomas in rats at different stages of tumor-growth by contrast enhanced MRI and dynamic susceptibility contrast (DSC) MRI at 7 Tesla. The analyses included maps of relative cerebral blood volume (CBV) and signal recovery derived from DSC data over a time period of up to 35 days after tumor cell injections. Results In all rats tumor progression was accompanied by temporal and spatial changes in CBV and capillary permeability. A leakage of the blood-brain barrier (slow contrast enhancement) was observed as soon as the tumor became detectable on T2-weighted images. Interestingly, areas of strong capillary permeability (fast signal enhancement) were predominantly localized in the center of the tumor. In contrast, the tumor rim was dominated by an increased CBV and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology. Conclusion Substantial regional differences in the tumor highlight the importance of parameter maps in contrast or in addition to region-of-interest analyses. The data vividly illustrate how MRI including contrast-enhanced and DSC-MRI may contribute to a better understanding of tumor development. PMID:28005983
Schoknecht, Karl; Prager, Ofer; Vazana, Udi; Kamintsky, Lyn; Harhausen, Denise; Zille, Marietta; Figge, Lena; Chassidim, Yoash; Schellenberger, Eyk; Kovács, Richard; Heinemann, Uwe; Friedman, Alon
Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood-brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood-brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex.
Bidon, Tobias; Frosch, Christiane; Eiken, Hans G; Kutschera, Verena E; Hagen, Snorre B; Aarnes, Siv G; Fain, Steven R; Janke, Axel; Hailer, Frank
We report a new approach for molecular sex identification of extant Ursinae and Tremarctinae bears. Two Y-specific fragments (SMCY and 318.2) and one X-specific fragment (ZFX) are amplified in a multiplex PCR, yielding a double test for male-specific amplification and an internal positive control. The primers were designed and tested to be bear-specific, thereby minimizing the risk of cross-amplification in other species including humans. The high sensitivity and small amplicon sizes (100, 124, 160 base pairs) facilitate analysis of non-invasively obtained DNA material. DNA from tissue and blood as well as from 30 non-invasively collected hair and faeces yielded clear and easily interpretable results. The fragments were detected both by standard gel electrophoresis and automated capillary electrophoresis.
Takahashi, Satoshi; Tanizaki, Yoshio; Akaji, Kazunori; Kimura, Hiroaki; Katano, Takehiro; Suzuki, Kentaro; Mochizuki, Yoichi; Shidoh, Satoka; Nakazawa, Masaki; Yoshida, Kazunari; Mihara, Ban
The aim of the study was to evaluate the potential role of computed tomography perfusion (CTP) imaging in identifying hemodynamically compromised regions in patients with occlusive cerebrovascular disease. Twelve patients diagnosed with either occlusion or severe stenosis of the internal carotid artery or the M1 portion of the middle cerebral artery underwent CTP imaging. The data was analyzed by an automated ROI-determining software. Patients were classified into two subgroups: an asymptomatic group consisting of three patients in whom perfusion pressure distal to the site of occlusion/stenosis (PPdis) could be maintained in spite of the arterial occlusion/stenosis, and a symptomatic group consisting of nine patients in whom PPdis could not be maintained enough to avoid watershed infarction. Four CTP-related parameters were independently compared between the two groups. Significant differences were determined using a two-sample t-test. When statistically significant differences were identified, cut-off points were calculated using ROC curves. Analysis revealed statistically significant differences between the asymptomatic and symptomatic subgroups only in the measure of relCBV (p=0.028). Higher relCBV values were observed in the symptomatic subgroup. ROC curve analysis revealed 1.059 to be the optimal relCBV cut-off value for distinguishing between the asymptomatic and symptomatic subgroups. The data revealed that, in patients whose PPdis is maintained, relCBV remains around 1.00. Conversely, in patients whose PPdis decreased, relCBV increased. From these findings, we conclude that elevation of relCBV as observed using CTP imaging accurately reflects the extent of compensatory vasodilatation involvement and can identify hemodynamically compromised regions.
Klaessens, John H. G. M.; Noordmans, Herke Jan; de Roode, Rowland; Verdaasdonk, Rudolf M.
This study describes noninvasive noncontact methods to acquire and analyze functional information from the skin. Multispectral images at several selected wavelengths in the visible and near infrared region are collected and used in mathematical methods to calculate concentrations of different chromophores in the epidermis and dermis of the skin. This is based on the continuous wave Near Infrared Spectroscopy method, which is a well known non-invasive technique for measuring oxygenation changes in the brain and in muscle tissue. Concentration changes of hemoglobin (dO2Hb, dHHb and dtHb) can be calculated from light attenuations using the modified Lambert Beer equation. We applied this technique on multi-spectral images taken from the skin surface using different algorithms for calculating changes in O2Hb, HHb and tHb. In clinical settings, the imaging of local oxygenation variations and/or blood perfusion in the skin can be useful for e.g. detection of skin cancer, detection of early inflammation, checking the level of peripheral nerve block anesthesia, study of wound healing and tissue viability by skin flap transplantations. Images from the skin are obtained with a multi-spectral imaging system consisting of a 12-bit CCD camera in combination with a Liquid Crystal Tunable Filter. The skin is illuminated with either a broad band light source or a tunable multi wavelength LED light source. A polarization filter is used to block the direct reflected light. The collected multi-spectral imaging data are images of the skin surface radiance; each pixel contains either the full spectrum (420 - 730 nm) or a set of selected wavelengths. These images were converted to reflectance spectra. The algorithms were validated during skin oxygen saturation changes induced by temporary arm clamping and applied to some clinical examples. The initial results with the multi-spectral skin imaging system show good results for detecting dynamic changes in oxygen concentration. However, the
Xu, Xia; Smith, Stanton; Urban, Jill; Cui, Zhanfeng
pH is an important control parameter for maintenance of cell viability and for improving tissue functions during cell and tissue culture. pH monitoring during cell/tissue culture also provides valuable information on cell metabolic processes and living environment. In this study, an on-line, non-invasive pH monitoring system was developed for use during tissue/cell culture in a perfusion system, using an optical method. This device included light sources, light detectors, light guides and a flow cell. Phenol red was used as a pH indicator dye, and the ratio of light intensities at two wavelengths was measured at the same pH value. Low solution volume as low as around 10 microl could be used to detect pH. Compared to the conventional optical methods, this non-contact optical measurement can avoid the contamination of the tip of optical fibre during the long-term monitoring. It provides a possibility to do on-line monitoring and apply feed back control to maintain the culture environment at the desired conditions required for long-term cell/tissue culture.
Pack, Jed D.; Yin, Zhye; Xiong, Guanglei; Mittal, Priya; Dunham, Simon; Elmore, Kimberly; Edic, Peter M.; Min, James K.
Coronary Artery Disease (CAD) is the leading cause of death globally . Modern cardiac computed tomography angiography (CCTA) is highly effective at identifying and assessing coronary blockages associated with CAD. The diagnostic value of this anatomical information can be substantially increased in combination with a non-invasive, low-dose, correlative, quantitative measure of blood supply to the myocardium. While CT perfusion has shown promise of providing such indications of ischemia, artifacts due to motion, beam hardening, and other factors confound clinical findings and can limit quantitative accuracy. In this paper, we investigate the impact of applying a novel motion correction algorithm to correct for motion in the myocardium. This motion compensation algorithm (originally designed to correct for the motion of the coronary arteries in order to improve CCTA images) has been shown to provide substantial improvements in both overall image quality and diagnostic accuracy of CCTA. We have adapted this technique for application beyond the coronary arteries and present an assessment of its impact on image quality and quantitative accuracy within the context of dual-energy CT perfusion imaging. We conclude that motion correction is a promising technique that can help foster the routine clinical use of dual-energy CT perfusion. When combined, the anatomical information of CCTA and the hemodynamic information from dual-energy CT perfusion should facilitate better clinical decisions about which patients would benefit from treatments such as stent placement, drug therapy, or surgery and help other patients avoid the risks and costs associated with unnecessary, invasive, diagnostic coronary angiography procedures.
Aslam; Pejović-Milić, A.; Chettle, D. R.; McNeill, F. E.; Pysklywec, M. W.; Oudyk, J.
Manganese (Mn) is a nutrient essential for regulating neurological and skeletal functions in the human body, but it is also toxic when humans are excessively exposed to Mn. Blood (or serum/plasma) and other body fluids reflect only the most recent exposure and rapidly return to within normal ranges, even when there has been a temporary excursion in response to exposure. In this context, we have been developing a non-invasive measurement of Mn stored in bone, using in vivo neutron activation analysis. Following feasibility studies, a first pilot study, using neutron activation analysis to measure Mn in the bones of the hand of ten healthy male human subjects, was conducted with the approval of the concerned research ethics boards. The participants of this study had no known history of exposure to Mn. Two volunteers were excluded from this study due to technical problems with their measurements. The inverse variance weighted mean value of Mn/Ca for the participants of this study is 0.12 ± 0.68 µg Mn/g Ca which is comparable within uncertainties with the estimated range of 0.16 0.78 µg Mn/g Ca and mean value of 0.63 ± 0.30 µg Mn/g Ca derived from cadaver data. It is recommended to investigate the use of the diagnostic technique for in vivo measurements of workers exposed occupationally to excessive amounts of Mn who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. The technique needs further development to improve the precision of in vivo measurements in the non-exposed population.
Background Haemophilia A (HA) is the most severe sex-linked bleeding disorder that is characterized with non-controlled and often threatening Haemorrhage. Routine fetal sex determination in early pregnancy with Haemophilia is based on invasive procedures that can be dangerous to the mother and fetus. Aim The goal of this study is to present an improved assay for the non-invasive fetal sex determination using a Real-Time duplex PCR on the free fetal DNA (ffDNA) obtained from the maternal serum of the HA carriers. Materials and Methods Blood samples were eventually collected from 23 pregnant HA carriers between the 8th and 12th weeks of gestation, and after amplification by duplex-PCR of the single copy of Y chromosome-specific sequence (SRY), the product was then subjected to Real-Time PCR analysis. Results Data were compared with the outcome of chorionic villus sampling (CVS) and indicated that the SRY sequence was detected in 6 of 6 serum samples from male pregnancies and that sequence was absent in 9 samples where the fetus was female. The remaining samples determined without having the CVS positive samples. Conclusion We tried to develop a Real-Time duplex PCR for accurate diagnosis of fetal gender early in the pregnancy of HA carriers. This study has brought up two remarkable points, the first is the method’s improvement with high specificity in sex determination, especially in screening of prenatal sex-linked disorders in male gender and the second is that fresh serum samples would be a good source for this purpose, advocated by similar studies carried out in this regard. PMID:26393142
Polito, Anthony B; Goldstein, David L; Sanchez, Lylian; Cool, David R; Morris, Mariana
The objective was to characterize the urinary oxytocin (OT) system with the goal of using it as a biomarker for neurohypophyseal peptide secretion. We studied urinary OT secretion in mice under three conditions: (1) in OT gene deletion mice (OT -/-) which lack the ability to produce the peptide; (2) after arterial vascular infusion of OT and (3) after physiological stimulation with consumption of 2% sodium chloride. OT was measured by radioimmunoassay (RIA) and Surface-Enhanced Laser Desorption Ionization Time of Flight Mass Spectroscopy (SELDI TOF MS). In OT -/- mice (n=25), urinary OT levels were not detectable, while in OT +/+ mice (n=23) levels were 250.2+/-35.3 pg/ml. To evaluate blood/urine transfer, mice with chronic carotid arterial catheters were infused with saline or OT (5 or 20 pmol/min). Peak urine OT levels were 89+/-11.5 and 844+/-181 ng/ml in the low and high OT groups, respectively. Proteomic evaluation showed MS peaks, corresponding to OT ( approximately 1009 Da) and a related peptide ( approximately 1030 Da) with highest levels in mice infused with OT. Salt loading (5 days of 2% NaCl as drinking water) increased plasma osmolality (3.3%), increased plasma and urinary vasopressin (AVP), but caused no changes in OT. Thus, using non-invasive urine samples, we document that urinary OT and AVP can be used to monitor changes in peptide secretion. Urinary OT and AVP, as well as other urinary peptides, may provide a viable biomarker for peptide secretion and may be useful in clinical studies.
Weber, Thomas G.; Osl, Franz; Renner, Anja; Pöschinger, Thomas; Galbán, Stefanie; Rehemtulla, Alnawaz; Scheuer, Werner
High grade gliomas often possess an impaired blood-brain barrier (BBB) which allows delivery of large molecules to brain tumors. However, achieving optimal drug concentrations in brain tumors remains a significant hurdle for treating patients successfully. Thus, detailed investigations of drug activities in gliomas are needed. To investigate BBB penetration, pharmacodynamics and tumor retention kinetics, we studied an agonistic DR5 antibody in a brain tumor xenograft model to investigate a non-invasive imaging method for longitudinal monitoring of apoptosis induction by this antibody. Brain tumors were induced by intracranial (i.c.) implantation of a luciferase-expressing tumor cell line as a reporter. To quantify accumulation of anti-DR5 in brain tumors, we generated a dose response curve for apoptosis induction after i.c. delivery of fluorescence-labeled anti-DR5 at different dosages. Assuming 100% drug delivery after i.c. application, the amount of accumulated antibody after i.v. application was calculated relative to its apoptosis induction. We found that up to 0.20–0.97% of antibody delivered i.v. reached the brain tumor, but that apoptosis induction declined quickly within 24 hours. These results were confirmed by 3D fluorescence microscopy of antibody accumulation in explanted brains. Nonetheless, significant antitumor efficacy was documented after anti-DR5 delivery. We further demonstrated that antibody crossing the BBB was facilitated its impairment in brain tumors. These imaging methods enable the quantification of antibody accumulation and pharmacodynamics in brain tumors, offering a holistic approach for assessment of CNS targeting drugs. PMID:24509903
Vanstone, Meredith; Yacoub, Karima; Giacomini, Mita; Hulan, Danielle; McDonald, Sarah
Non-invasive prenatal testing (NIPT) via fetal DNA in maternal blood has been publicly funded in Ontario, Canada, for high-risk women since 2014. We solicited women's experiences and values related to this new health technology to describe how this test is currently being used in Ontario and to provide information about patient priorities to inform future policy decisions about the use of NIPT. Guided by constructivist grounded theory methodology, we interviewed 38 women who had diverse personal experiences with NIPT. Participants' accounts of their values for decision making about NIPT heavily relied on three mutually modulating factors: timing, accuracy, and risk. The values expressed by women conflict with the way that publicly funded NIPT has typically been implemented in Ontario. We offer recommendations for how NIPT might be integrated into prenatal care pathways in a way more consistent with women's values.
Sorvoja, H.S.S.; Myllylae, T S; Myllylae, Risto A; Kirillin, M Yu; Sergeeva, Ekaterina A; Elseoud, A A; Nikkinen, J; Tervonen, O; Kiviniemi, V
A non-invasive device for measuring blood oxygen variations in human brain is designed, implemented, and tested for MRI compatibility. The device is based on principles of near-IR reflectometry; power LEDs serve as sources of probing radiation delivered to patient skin surface through optical fibres. Numerical Monte Carlo simulations of probing radiation propagation in a multilayer brain model are performed to evaluate signal levels at different source - detector separations at three operation wavelengths and an additional wavelength of 915 nm. It is shown that the device can be applied for brain activity studies using power LEDs operating at 830 and 915 nm, while employment of wavelength of 660 nm requires an increased probing power. Employment of the wavelength of 592 nm in the current configuration is unreasonable. (application of lasers and laser-optical methods in life sciences)
Yu, Huidan (Whitney); Chen, Rou; An, Senyou; McDonough, James; Gelfand, Bradley; Yao, Jun
The development of retinal disease is inextricably linked to defects in the choroidal blood supply. However, to date a description of the hemodynamics in the human choroidal circulation is lacking. Through high resolution choroidal vascular network mapped from immunofluorescent labeling and confocal microscopy of human cadaver donor eyes. We noninvasively quantify hemodynamics including velocity, pressure, and wall-shear stress (WSS) in choriocapillaries through mesoscale modeling and GPU-accelerated fast computation. This is the first-ever map of hemodynamic parameters (WSS, pressure, and velocity) in anatomically accurate human choroidal vasculature in health and disease. The pore scale simulation results are used to evaluate porous media models with the same porosity and boundary conditions. School of Medicine, Indiana University.
Choi, Myunghwan; Choi, Chulhee
For a systemically administered drug to act, it first needs to cross the vascular wall. This step represents a bottleneck for drug development, especially in the brain or retina, where tight junctions between endothelial cells form physiological barriers. Here, we demonstrate that femtosecond pulsed laser irradiation focused on the blood vessel wall induces transient permeabilization of plasma. Nonlinear absorption of the pulsed laser enabled the noninvasive modulation of vascular permeability with high spatial selectivity in three dimensions. By combining this method with systemic injection, we could locally deliver molecular probes in various tissues, such as brain cortex, meninges, ear, striated muscle, and bone. We suggest this method as a novel delivery tool for molecular probes or drugs.
Raoof, Mustafa; Curley, Steven A.
Targeted biological therapies for hepatocellular cancer have shown minimal improvements in median survival. Multiple pathways to oncogenesis leading to rapid development of resistance to such therapies is a concern. Non-invasive radiofrequency field-induced targeted hyperthermia using nanoparticles is a radical departure from conventional modalities. In this paper we underscore the need for innovative strategies for the treatment of hepatocellular cancer, describe the central paradigm of targeted hyperthermia using non-invasive electromagnetic energy, review the process of characterization and modification of nanoparticles for the task, and summarize data from cell-based and animal-based models of hepatocellular cancer treated with non-invasive RF energy. Finally, future strategies and challenges in bringing this modality from bench to clinic are discussed. PMID:21994866
Chalah, Moussa A.; Lefaucheur, Jean-Pascal; Ayache, Samar S.
Essential tremor (ET) is among the most frequent movement disorders. It usually manifests as a postural and kinematic tremor of the arms, but may also involve the head, voice, lower limbs, and trunk. An oscillatory network has been proposed as a neural correlate of ET, and is mainly composed of the olivocerebellar system, thalamus, and motor cortex. Since pharmacological agents have limited benefits, surgical interventions like deep brain stimulation are the last-line treatment options for the most severe cases. Non-invasive brain stimulation techniques, particularly transcranial magnetic or direct current stimulation, are used to ameliorate ET. Their non-invasiveness, along with their side effects profile, makes them an appealing treatment option. In addition, peripheral stimulation has been applied in the same perspective. Hence, the aim of the present review is to shed light on the emergent use of non-invasive central and peripheral stimulation techniques in this interesting context. PMID:26635516
Esquinas, A M; Jover, J L; Úbeda, A; Belda, F J
Non-invasive mechanical ventilation is a method of ventilatory assistance aimed at increasing alveolar ventilation, thus achieving, in selected subjects, the avoidance of endotracheal intubation and invasive mechanical ventilation, with the consequent improvement in survival. There has been a systematic review and study of the technical, clinical experiences, and recommendations concerning the application of non-invasive mechanical ventilation in the pre- and intraoperative period. The use of prophylactic non-invasive mechanical ventilation before surgery that involves significant alterations in the ventilatory function may decrease the incidence of postoperative respiratory complications. Its intraoperative use will mainly depend on the type of surgery, type of anaesthetic technique, and the clinical status of the patient. Its use allows greater anaesthetic depth without deterioration of oxygenation and ventilation of patients.
Myocardial perfusion single photon emission-computed tomography (MPS) has been one of the most important and common non-invasive diagnostic cardiac test. Gated MPS provides simultaneous assessment of myocardial perfusion and function with only one study. With appropriate attention to the MPS techniques, appropriate clinical utilization and effective reporting, gated MPS will remain a useful diagnostic test for many years to come. The aim of this article is to review the basic techniques of MPS, a simplified systematic approach for study interpretation, current clinical indications and reporting. After reading this article the reader should develop an understanding of the techniques, interpretation, current clinical indications and reporting of MPS studies.
Kim, MinWoo; Abbey, Craig K.; Insana, Michael F.
Enhanced blood perfusion in a tissue mass is an indication of neo-vascularity and a sign of a potential malignancy. Ultrasonic pulsed-Doppler imaging is a preferred modality for noninvasive monitoring of blood flow. However, the weak blood echoes and disorganized slow flow make it difficult to detect perfusion using standard methods without the expense and risk of contrast enhancement. Our research measures the efficiency of conventional power-Doppler (PD) methods at discriminating flow states by comparing measurement performance to that of an ideal discriminator. ROC analysis applied to the experimental results shows that power Doppler methods are just 30-50 % efficient at perfusion flows less than 1ml/min, suggesting an opportunity to improve perfusion assessment through signal processing. A new perfusion estimator is proposed by extending the statistical discriminator approach. We show that 2-D perfusion color imaging may be enhanced using this approach.
Narayan, E. J.
Non-invasive endocrinology utilizes non-invasive biological samples (such as faeces, urine, hair, aquatic media, and saliva) for the quantification of hormones in wildlife. Urinary-based enzyme immunoassay (EIA) and radio-immunoassay have enabled the rapid quantification of reproductive and stress hormones in amphibians (Anura: Amphibia). With minimal disturbance, these methods can be used to assess the ovarian and testicular endocrine functions as well as physiological stress in captive and free-living populations. Non-invasive endocrine monitoring has therefore greatly advanced our knowledge of the functioning of the stress endocrine system (the hypothalamo–pituitary–interrenal axis) and the reproductive endocrine system (the hypothalamo–pituitary–gonadal axis) in the amphibian physiological stress response, reproductive ecology, health and welfare, and survival. Biological (physiological) validation is necessary for obtaining the excretory lag time of hormone metabolites. Urinary-based EIA for the major reproductive hormones, estradiol and progesterone in females and testosterone in males, can be used to track the reproductive hormone profiles in relationship to reproductive behaviour and environmental data in free-living anurans. Urinary-based corticosterone metabolite EIA can be used to assess the sublethal impacts of biological stressors (such as invasive species and pathogenic diseases) as well as anthropogenic induced environmental stressors (e.g. extreme temperatures) on free-living populations. Non-invasive endocrine methods can also assist in the diagnosis of success or failure of captive breeding programmes by measuring the longitudinal patterns of changes in reproductive hormones and corticosterone within captive anurans and comparing the endocrine profiles with health records and reproductive behaviour. This review paper focuses on the reproductive and the stress endocrinology of anurans and demonstrates the uses of non-invasive endocrinology
Hunold, Peter; Schlosser, Thomas; Barkhausen, Jörg
Coronary artery disease (CAD) with its clinical appearance of stable or unstable angina and acute myocardial infarction is the leading cause of death in developed countries. In view of increasing costs and the rising number of CAD patients, there has been a major interest in reliable non-invasive imaging techniques to identify CAD in an early (i.e. asymptomatic) stage. Since myocardial perfusion deficits appear very early in the "ischemic cascade", a major breakthrough would be the non-invasive quantification of myocardial perfusion before functional impairment might be detected. Therefore, there is growing interest in other, target-organ-specific parameters, such as relative and absolute myocardial perfusion imaging. Magnetic resonance (MR) imaging has been proven to offer attractive concepts in this respect. However, some important difficulties have not been resolved so far, which still causes uncertainty and prevents the broad application of MR perfusion imaging in a clinical setting. This review explores recent technical developments in MR hardware, software and contrast agents, as well as their impact on the current and future clinical status of MR imaging of first-pass myocardial perfusion imaging.
Wong, Grace Lai-Hung; Espinosa, Wendell Zaragoza
Owing to the high prevalence of various chronic liver diseases, cirrhosis is one of the leading causes of morbidity and mortality worldwide. In recent years, the development of non-invasive tests of fibrosis allows accurate diagnosis of cirrhosis and reduces the need for liver biopsy. In this review, we discuss the application of these non-invasive tests beyond the diagnosis of cirrhosis. In particular, their role in the selection of patients for hepatocellular carcinoma surveillance and varices screening is highlighted. PMID:26523265
Matousek, Pavel; Stone, Nicholas
Raman spectroscopy has recently undergone major advances in the area of deep non-invasive characterisation of biological tissues. The progress stems from the development of spatially offset Raman spectroscopy (SORS) and renaissance of transmission Raman spectroscopy permitting the assessment of diffusely scattering samples at depths several orders of magnitude deeper than possible with conventional Raman spectroscopy. Examples of emerging applications include non-invasive diagnosis of bone disease, cancer and monitoring of glucose levels. This article reviews this fast moving field focusing on recent developments within the medical area.
Alfonso Megido, Joaquín; González Franco, Alvaro
When acute heart failure progresses and there is acute cardiogenic pulmonary edema, routine therapeutic measures should be accompanied by other measures that help to correct oxygenation of the patient. The final and most drastic step is mechanical ventilation. Non-invasive ventilation has been developed in the last few years as a method that attempts to improve oxygenation without the need for intubation, thus, in theory, reducing morbidity and mortality in these patients. The present article describes the controversies surrounding the results of this technique and discusses its indications. The article also discusses how to start non-invasive ventilation in patients with acute pulmonary edema from a practical point of view.
A rapid test for an infectious disease that can be used at point-of-care at a physician's office, a pharmacy, or in the field is critical for the prompt and appropriate therapeutic intervention. Ultimately by treating infections early on will decrease transmission of the pathogen. In contrast to metabolic diseases or cancer where multiple biomarkers are required, infectious disease targets (e.g. antigen, antibody, nucleic acid) are simple and specific for the pathogen causing the disease. Our laboratory has focused on three major infectious disease; HIV, Tuberculosis, and Malaria. These diseases are pandemic in much of the world thus putting natives, tourists and military personnel at risk for becoming infected, and upon returning to the U.S., transmitting these diseases to their contacts. Our devices are designed to detect antigens, antibodies or nucleic acids in blood or saliva samples in less than 30 minutes. An overview describing the current status of each of the three diagnostic platforms is presented. These microfluidic point-of-care devices will be relatively inexpensive, disposable, and user friendly.
Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...
could result in significant artifacts. The first part of this thesis addresses the first limitation by introducing the Recursive Echo Strain Filter (RESF) as a new temperature reconstruction model which largely corrects for the spatial inconsistencies resulting from the infinitesimal model. The performance of this model is validated using the data collected during sub therapeutic temperature changes in the tissue mimicking phantom as well as ex vivo tissue blocks. The second part of this thesis deals with in vivo ultrasound thermography. Tissue deformations caused by natural motions (e.g. respiration, gasping, blood pulsation etc) can create non-thermal changes to the ultrasound echoes which are not accounted for in the derivation of physical model for temperature estimation. These fluctuations can create severe artifacts in the estimated temperature field. Using statistical signal processing techniques an adaptive method is presented which takes advantage of the localized and global availability of these interference patterns and use this data to enhance the estimated temperature in the region of interest. We then propose a model based technique for continuous tracking of temperature in the presence of natural motion and deformation. The method uses the direct discretization of the transient bioheat equation to derive a state space model of temperature change. This model is then used to build a linear estimator based on the Kalman filtering capable of robust estimation of temperature change in the presence of tissue motion and deformation. The robustness of the adaptive and model-based models in removing motion and deformation artifacts is demonstrated using data from in vivo experiments. Both methods are shown to provide effective cancellation of the artifacts with minimal effect on the expected temperature dynamics.
Masa, Juan F; Corral, Jaime; Caballero, Candela; Barrot, Emilia; Terán-Santos, Joaquin; Alonso-Álvarez, Maria L; Gomez-Garcia, Teresa; González, Mónica; López-Martín, Soledad; De Lucas, Pilar; Marin, José M; Marti, Sergi; Díaz-Cambriles, Trinidad; Chiner, Eusebi; Egea, Carlos; Miranda, Erika; Mokhlesi, Babak; García-Ledesma, Estefanía; Sánchez-Quiroga, M-Ángeles; Ordax, Estrella; González-Mangado, Nicolás; Troncoso, Maria F; Martinez-Martinez, Maria-Ángeles; Cantalejo, Olga; Ojeda, Elena; Carrizo, Santiago J; Gallego, Begoña; Pallero, Mercedes; Ramón, M Antonia; Díaz-de-Atauri, Josefa; Muñoz-Méndez, Jesús; Senent, Cristina; Sancho-Chust, Jose N; Ribas-Solís, Francisco J; Romero, Auxiliadora; Benítez, José M; Sanchez-Gómez, Jesús; Golpe, Rafael; Santiago-Recuerda, Ana; Gomez, Silvia; Bengoa, Mónica
Background Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. Methods Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. Results A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of −6 (95% CI −7.7 to −4.2) mm Hg versus −2.8 (95% CI −4.3 to −1.3) mm Hg, (p<0.001) and serum bicarbonate of −3.4 (95% CI −4.5 to −2.3) versus −1 (95% CI −1.7 to −0.2 95% CI) mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. Conclusions NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long
Sharma, Amit M.; Sharma, Namita; Nat, Amritpal; Rane, Meghan; Endy, Timothy P.
Madura foot is a chronic infection caused by fungus and/or bacteria. Traditionally, treatment has been surgical debridement or amputation. Non-invasive management with long-term antimicrobials alone has been reported as successful. We report a case of Madura foot in a Somali refugee successfully managed with oral posaconazole and ciprofloxacin. PMID:25349373
According to the classical international guidelines, non-invasive ventilation is contraindicated in hypercapnic encephalopathy syndrome (HES) due to the poor compliance to ventilatory treatment of confused/agitated patients and the risk of aspirative pneumonia related to lack of airways protection. As a matter of fact, conventional mechanical ventilation has been recommended as "golden standard" in these patients. However, up to now there are not controlled data that have demonstrated in HES the advantage of conventional mechanical ventilation vs non-invasive ventilation. In fact, patients with altered mental status have been systematically excluded from the randomised and controlled trials performed with non-invasive ventilation in hypercapnic acute respiratory failure. Recent studies have clearly demonstrated that an initial cautious NPPV trial in selected HES patients may be attempt as long as there are no other contraindications and the technique is provided by experienced caregivers in a closely monitored setting where ETI is always readily available. The purpose of this review is to report the physiologic rationale, the clinical feasibility and the still open questions about the careful use of non-invasive ventilation in HES as first-line ventilatory strategy in place of conventional mechanical ventilation via endotracheal intubation.
Chaturvedi, P; Taguchi, M; Burrs, S L; Hauser, B A; Salim, W W A W; Claussen, J C; McLamore, E S
Oxygen plays a critical role in plant metabolism, stress response/signaling, and adaptation to environmental changes (Lambers and Colmer, Plant Soil 274:7-15, 2005; Pitzschke et al., Antioxid Redox Signal 8:1757-1764, 2006; Van Breusegem et al., Plant Sci 161:405-414, 2001). Reactive oxygen species (ROS), by-products of various metabolic pathways in which oxygen is a key molecule, are produced during adaptation responses to environmental stress. While much is known about plant adaptation to stress (e.g., detoxifying enzymes, antioxidant production), the link between ROS metabolism, O2 transport, and stress response mechanisms is unknown. Thus, non-invasive technologies for measuring O2 are critical for understanding the link between physiological O2 transport and ROS signaling. New non-invasive technologies allow real-time measurement of O2 at the single cell and even organelle levels. This review briefly summarizes currently available (i.e., mainstream) technologies for measuring O2 and then introduces emerging technologies for measuring O2. Advanced techniques that provide the ability to non-invasively (i.e., non-destructively) measure O2 are highlighted. In the near future, these non-invasive sensors will facilitate novel experimentation that will allow plant physiologists to ask new hypothesis-driven research questions aimed at improving our understanding of physiological O2 transport.
van Kleunen, Mark; Weber, Ewald; Fischer, Markus
A major aim in ecology is identifying determinants of invasiveness. We performed a meta-analysis of 117 field or experimental-garden studies that measured pair-wise trait differences of a total of 125 invasive and 196 non-invasive plant species in the invasive range of the invasive species. We tested whether invasiveness is associated with performance-related traits (physiology, leaf-area allocation, shoot allocation, growth rate, size and fitness), and whether such associations depend on type of study and on biogeographical or biological factors. Overall, invasive species had significantly higher values than non-invasive species for all six trait categories. More trait differences were significant for invasive vs. native comparisons than for invasive vs. non-invasive alien comparisons. Moreover, for comparisons between invasive species and native species that themselves are invasive elsewhere, no trait differences were significant. Differences in physiology and growth rate were larger in tropical regions than in temperate regions. Trait differences did not depend on whether the invasive alien species originates from Europe, nor did they depend on the test environment. We conclude that invasive alien species had higher values for those traits related to performance than non-invasive species. This suggests that it might become possible to predict future plant invasions from species traits.
Edwards, Perry S.
Fiber-optic based diffuse reflectance spectroscopy (DRS) is shown to be a highly specific and highly sensitive method for non-invasive detection of various cancers (e.g. cervical and oral) as well as many other diseases. Fiber-optic DRS diagnosis relies on non-invasive biomarker detection (e.g. oxy- and deoxy-hemoglobin) and can be done without the need for sophisticated laboratory analysis of samples. Thus, it is highly amenable for clinical adoption especially in resource scarce regions that have limited access to such developed laboratory infrastructure. Despite the demonstrated effectiveness of fiber-optic DRS, such systems remain cost prohibitive in many of these regions, mainly due to the use of bulky and expensive spectrometers. Here, a fiber-optic DRS system is coupled to a smartphone spectrometer and is proposed as a low-cost solution for non-invasive tissue hemoglobin sensing. The performance of the system is assessed by measuring tissue phantoms with varying hemoglobin concentrations. A DRS retrieval algorithm is used to extract hemoglobin parameters from the measurements and determine the accuracy of the system. The results are then compared with those of a previously reported fiber-optic DRS system which is based on a larger more expensive spectrometer system. The preliminary results are encouraging and indicate the potential of the smartphone spectrometer as a viable low-cost option for non-invasive tissue hemoglobin sensing.
This was the second year that our breath colleagues organized a networking session at the Pittsburgh Conference and Exposition or ''PittCon'' (http://www.pincon.org/).This time it was called "Non-invasive Biomedical Analysis" to broaden the scope a bit, but the primary focus rema...
Moissidou, Despina; Day, Jasmine; Shin, Dong Hoon; Bianucci, Raffaella
Advances in the application of non invasive techniques to mummified remains have shed new light on past diseases. The virtual inspection of a corpse, which has almost completely replaced classical autopsy, has proven to be important especially when dealing with valuable museum specimens. In spite of some very rewarding results, there are still many open questions. Non invasive techniques provide information on hard and soft tissue pathologies and allow information to be gleaned concerning mummification practices (e.g., ancient Egyptian artificial mummification). Nevertheless, there are other fields of mummy studies in which the results provided by non invasive techniques are not always self-explanatory. Reliance exclusively upon virtual diagnoses can sometimes lead to inconclusive and misleading interpretations. On the other hand, several types of investigation (e.g., histology, paleomicrobiology, and biochemistry), although minimally invasive, require direct contact with the bodies and, for this reason, are often avoided, particularly by museum curators. Here we present an overview of the non invasive and invasive techniques currently used in mummy studies and propose an approach that might solve these conflicts.
Williams, Julie A; Imamura, Marta; Fregni, Felipe
Brain stimulation for the treatment of neuropsychiatric diseases has been used for more than 50 years. Although its development has been slow, current advances in the techniques of brain stimulation have improved its clinical efficacy. The use of non-invasive brain stimulation has significant advantages, such as not involving surgical procedures and having relatively mild adverse effects. In this paper we briefly review the use of 2 non-invasive brain stimulation techniques, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), as therapeutic approaches in physical and rehabilitation medicine. We also compare the effects of non-invasive central nervous system stimulation with techniques of non-invasive peripheral electrical stimulation, in order to provide new insights for future developments. Although the outcomes of these initial trials include some conflicting results, the evidence supports that rTMS and tDCS might have a therapeutic value in different neurological conditions. Studies published within the last year have examined new approaches of stimulation, such as longer intensities of stimulation, new electrode sizes for tDCS, novel coils for stimulation of deeper areas, and new frequencies of stimulation for rTMS. These new approaches need to be tested in larger clinical trials in order to determine whether they offer significant clinical effects.
Various obstacles are encountered by mammalian spermatozoa during their journey through the female genital tract, and only few or none will reach the site of fertilization. Currently, there are limited technical approaches for non-invasive investigation of spermatozoa migration after insemination. A...
Lambrecht, R.M.; Packer, S.
There is described an apparatus and method for diagnosing ocular cancer that is both non-invasive and accurate which comprises two radiation detectors positioned before each of the patient's eyes which will measure the radiation level produced in each eye after the administration of a tumor-localizing radiopharmaceutical such as gallium-67.
Moissidou, Despina; Day, Jasmine; Shin, Dong Hoon; Bianucci, Raffaella
Advances in the application of non invasive techniques to mummified remains have shed new light on past diseases. The virtual inspection of a corpse, which has almost completely replaced classical autopsy, has proven to be important especially when dealing with valuable museum specimens. In spite of some very rewarding results, there are still many open questions. Non invasive techniques provide information on hard and soft tissue pathologies and allow information to be gleaned concerning mummification practices (e.g., ancient Egyptian artificial mummification). Nevertheless, there are other fields of mummy studies in which the results provided by non invasive techniques are not always self-explanatory. Reliance exclusively upon virtual diagnoses can sometimes lead to inconclusive and misleading interpretations. On the other hand, several types of investigation (e.g., histology, paleomicrobiology, and biochemistry), although minimally invasive, require direct contact with the bodies and, for this reason, are often avoided, particularly by museum curators. Here we present an overview of the non invasive and invasive techniques currently used in mummy studies and propose an approach that might solve these conflicts. PMID:26345295
Chandra, Malavika; Vishwanath, Karthik; Fichter, Greg D.; Liao, Elly; Hollister, Scott J.; Mycek, Mary-Ann
A method to non-invasively and quantitatively characterize thick biological tissues by combining both experimental and computational approaches in tissue optical spectroscopy was developed and validated on fifteen porcine articular cartilage (AC) tissue samples. To the best of our knowledge, this study is the first to couple non-invasive reflectance and fluorescence spectroscopic measurements on freshly harvested tissues with Monte Carlo computational modeling of time-resolved propagation of both excitation light and multi-fluorophore emission. For reflectance, quantitative agreement between simulation and experiment was achieved to better than 11%. Fluorescence data and simulations were used to extract the ratio of the absorption coefficients of constituent fluorophores for each measured AC tissue sample. This ratio could be used to monitor relative changes in concentration of the constituent fluorophores over time. The samples studied possessed the complexity and variability not found in artificial tissue-simulating phantoms and serve as a model for future optical molecular sensing studies on tissue engineered constructs intended for use in human therapeutics. An optical technique that could non-invasively and quantitatively assess soft tissue composition or physiologic status would represent a significant advance in tissue engineering. Moreover, the general approach described here for optical characterization should be broadly applicable to quantitative, non-invasive molecular sensing applications in complex, three-dimensional biological tissues.
Yu, Xuyao; Liu, Rong; Yu, Hui; Wang, Jiao; Wang, Jun; Xu, Kexin
Near-infrared spectroscopy is often used for the non-invasive detection of composition in the human body, such as that of blood glucose and haemoglobin, due to its high penetration depth into tissues. Although it is feasible to position the optical probe precisely, contact situation between probe and human tissues is a difficult problem to determine because of physiological tremor and mechanical performance of bio-soft tissue. Here, we proposed a novel estimation method for the situation between the optical probe and tissue surfaces based on the dynamic auto-correlation matrix of two-dimensional correlation spectroscopy (2DCOS) and radar chart. The diffuse reflectance spectra from the left palm of 4 healthy volunteers were collected while the optical probe gradually approached and pressed bio-tissues with a custom-design controlling device. 2DCOS in the wavelength with lower absorption (1000-1400 nm) was calculated under the perturbation of relative-distance and contact pressure between the optical probe and tissue surface. The synchronous 2DCOS showed that the surface reflection and diffuse reflectance were greatly affected by the contact conditions in 1100 nm, 1220 nm, and 1300 nm. Then the dynamic auto-correlation matrix of 2DCOS was established for the adjacent spectra, and the significant difference wavelengths were used to build radar charts to determine the critical contact situation visually. Results showed that the maximum variations of dynamic auto-correlation matrix appeared at near 1300 nm, and the relative distance between the probe and tissue corresponding to the critical contact state can be easily observed with radar charts with 0.25 mm uncertainty, which was consistent with the self-feeling of each volunteer. So this method can be applied to exactly determine the optimal measurement status for the non-invasive body composition detection in vivo. It is important for the design of human-machine interface and the accuracy improvement of body
Bernard, Alfred . E-mail: firstname.lastname@example.org; Carbonnelle, Sylviane; Nickmilder, Marc; Burbure, Claire de
To date, airways injury or inflammation caused by air pollutants has been evaluated mainly by analysis of bronchoalveolar lavage, an invasive technique totally unsuitable to children. The assessment of respiratory risks in this particularly vulnerable population has thus for a long time relied on spirometric tests and self-reported symptoms which are relatively late and inaccurate indicators of lung damage. Research in the field of biomarkers is now opening new perspectives with the development of non-invasive tests allowing to monitor inflammation and damage in the deep lung. Blood tests measuring lung-specific proteins (pneumoproteins) such as Clara cell protein (CC16) and surfactant-associated proteins (A, B or D) are now available to evaluate the permeability and/or the cellular integrity of the pulmonary epithelium. The application of these tests to children has recently led to the discovery of a lung epithelium hyperpermeability caused by trichloramine (nitrogen trichloride), an irritant gas contaminating the air of indoor-chlorinated pools. Serum CC16 can also serve to detect increases of airway permeability during short-term exposures to ambient ozone. Indicators measurable in exhaled air such as nitric oxide (NO) appear more useful to detect airway inflammation. By applying the exhaled NO test to children attending summer camps, we recently found that ambient ozone produces an acute inflammatory response in children from levels slightly lower than current air quality guidelines. In a study exploring the links between atopy, asthma, and exposure to chlorination products in indoor pools, we also found that the exhaled NO test can serve to detect the chronic airway inflammation associated with excessive exposure to trichloramine. Lung-specific proteins measurable in serum and markers in exhaled air represent sensitive tools that can be used to assess non-invasively the effects of air pollutants on the respiratory tract of children.
Neeb, Daniel; Kunz, Rainer Peter; Ley, Sebastian; Szábo, Gábor; Strauss, Ludwig G; Kauczor, Hans-Ulrich; Kreitner, Karl-Friedrich; Schreiber, Laura Maria
Validation of quantification of pulmonary blood flow (PBF) with dynamic, contrast-enhanced MRI is still missing. A possible reason certainly lies in difficulties based on the nonlinear dependence of signal intensity (SI) from contrast agent (CA) concentration. Both aspects were addressed in this study. Nine healthy pigs were examined by first-pass perfusion MRI using gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) and H(2)(15)O positron emission tomography (PET) imaging. Calculations of hemodynamic parameters were based on a one-compartment model (MR) and a two-compartment model (PET). Simulations showed a significant error when assuming a linear relation between MR SI and CA dose in the arterial input function (AIF), even at low doses of 0.025 mmol/kg body weight (BW). To correct for nonlinearity, a calibration curve was calculated on the basis of the signal equation. The required accuracy of equation parameters (like longitudinal relaxation time) was evaluated. Error analysis estimates <5% over-/underestimation of the corrected SI. Comparison of PET and MR flow values yielded a significant correlation (P < 0.001) in dorsal regions where signal-to-noise ratio (SNR) was sufficient. Changes in PBF due to the correction method were significant (P < 0.001) and resulted in a better agreement: mean values (standard deviation) in units of ml/min/100 ml lung tissue were 59 (15) for PET, 112 (28) for uncorrected MRI, and 80 (21) for corrected MRI.
Takahashi, Satoshi; Tanizaki, Yoshio; Kimura, Hiroaki; Akaji, Kazunori; Kano, Tadashige; Suzuki, Kentaro; Takayama, Youhei; Kanzawa, Takao; Shidoh, Satoka; Nakazawa, Masaki; Yoshida, Kazunari; Mihara, Ban
Cerebral blood flow (CBF) data obtained by computed tomography perfusion (CTP) imaging have been shown to be qualitative data rather than quantitative, in contrast with data obtained by other imaging methods, such as xenon CT (XeCT) imaging. Thus, interpatient comparisons of CBF values themselves obtained by CTP may be inaccurate. In this study, we have compared CBF ratios as well as CBF values obtained from CTP-CBF data to those obtained from XeCT-CBF data for the same patients to determine CTP-CBF parameters that can be used for interpatient comparisons. The data used in the present study were obtained as volume data using 320-row CT. The volume data were applied to an automated region of interest-determining software (3DSRT, version 3.5.2 ) and converted to 59 slices of 2 mm interval standardized images. In the present study, we reviewed 10 patients with occlusive cerebrovascular diseases (CVDs) undergoing both CTP and XeCT in the same period. Our study shows that ratios of CBF measurements, such as hemodynamic stress distribution (perforator-to-cortical flow ratio of middle cerebral artery [MCA] region) or the left/right ratio for the region of the MCA, calculated using CTP data have been shown to correlate well with the same ratios calculated using XeCT data. These results suggest that such CBF ratios could be useful for generating interpatient comparisons of CTP-CBF data obtained by 320-row CT among patients with occlusive CVD.
Ley, Sebastian; Stadthalter, Miriam; Link, Dietmar; Laqua, Daniel; Husar, Peter
An optical phantom of the maternal abdomen during pregnancy is an appropriate test environment to evaluate a non-invasive system for fetal pulse oximetry. To recreate the optical properties of maternal tissue, fetal tissue and blood suitable substitutes are required. For this purpose, phantom materials are used, which consist of transparent silicone or water as host material. Cosmetic powder and India ink are investigated as absorbing materials, whereas titanium dioxide particles are examined as scattering medium. Transmittance and reflectance measurements of the samples were performed in the spectral range from 600 nm to 900 nm using integrating sphere technique. The scattering and absorption coefficients and the anisotropy factor were determined using Kubelka-Munk theory. The results were used to compute the required mixture ratios of the respective components to replicate the optical properties of maternal tissue, fetal tissue and blood, and corresponding samples were produced. Their optical properties were investigated in the same manner as mentioned above. The results conform to the values of various types of tissues and blood given in the scientific literature.
Bindra, R M; Imhof, R E; Andrew, J J; Cummins, P G; Eccleston, G M
Summary Opto-thermal transient radiometry (OTTER) is a non-invasive measurement technique, well suited for in vivo skin research. Its excitation and detection wavelengths can be selected to give a high sensitivity to stratum corneum hydration. This is demonstrated with measurements of hydration changes resulting from occlusion with a neoprene cover and with a topical application of an occlusive preparation. In the former case, the hydration was found to recover to normal levels upon exposure to atmospheric conditions in a characteristic time of 15 min. In the latter case, a topical application of petroleum jelly was found to lead to a doubling of stratum corneum hydration over 2h. This ability to measure hydration changes in the presence of topical hydrating agents is thought to be a particularly valuable property of the OTTER technique. With a different choice of excitation and detection wavelengths, OTTER can be used to measure skin thickness, from the surface down to the vascular bed. This technique was used to measure a skin thickness map of the ventral surface of the forearm of a volunteer, showing distinct thickening near the wrist and ulna. Another use of this technique is the study of changes in subcutaneous blood distribution associated with erythema. As a demonstration of this, blood distribution changes brought about by the topical application of a salicylate/nicotinate preparation were studied. The main finding is that the subcutaneous blood spreads towards the surface, with the mean depth decreasing from 63 mum to 55mum.
Pasamontes, Alberto; Aksenov, Alexander A; Schivo, Michael; Rowles, Teri; Smith, Cynthia R; Schwacke, Lori H; Wells, Randall S; Yeates, Laura; Venn-Watson, Stephanie; Davis, Cristina E
Health assessments of wild cetaceans can be challenging due to the difficulty of gaining access to conventional diagnostic matrices of blood, serum and others. While the non-invasive detection of metabolites in exhaled breath could potentially help to address this problem, there exists a knowledge gap regarding associations between known disease states and breath metabolite profiles in cetaceans. This technology was applied to the largest marine oil spill in U.S. history (The 2010 Deepwater Horizon oil spill in the Gulf of Mexico). Comprehensive analysis was performed to test for associations between the exhaled breath metabolome and sonographic lung abnormalities as well as hematological, serum biochemical, and endocrine hormone parameters. Importantly, metabolites consistent with chronic inflammation, such as products of lung epithelial cellular breakdown and arachidonic acid cascade metabolites were associated with sonographic evidence of lung consolidation. Exhaled breath condensate (EBC) metabolite profiles also correlated with serum hormone concentrations (cortisol and aldosterone), hepatobiliary enzyme levels, white blood cell counts, and iron homeostasis. The correlations among breath metabolites and conventional health measures suggest potential application of breath sampling for remotely assessing health of wild cetaceans. This methodology may hold promise for large cetaceans in the wild for which routine collection of blood and respiratory anomalies are not currently feasible.
Wang, Ling; Mohan, Chandra
This article reviews the application of contrast-enhanced ultrasound (CEUS) in gauging renal microvascular perfusion in diverse renal diseases. The unique nature of the contrast agents used in CEUS provides real-time and quantitative imaging of the vasculature. In addition to the traditional use of CEUS for evaluation of kidney masses, it also emerges as a safe and effective imaging approach to assess microvascular perfusion in diffuse renal lesions, non-invasively. Although the precise CEUS parameters that may best predict disease still warrant systematic evaluation, animal models and limited clinical trials in humans raise hopes that CEUS could outcompete competing modalities as a first-line tool for assessing renal perfusion non-invasively, even in ailments such as acute kidney injury and chronic kidney disease.
Abstract This article reviews the application of contrast-enhanced ultrasound (CEUS) in gauging renal microvascular perfusion in diverse renal diseases. The unique nature of the contrast agents used in CEUS provides real-time and quantitative imaging of the vasculature. In addition to the traditional use of CEUS for evaluation of kidney masses, it also emerges as a safe and effective imaging approach to assess microvascular perfusion in diffuse renal lesions, non-invasively. Although the precise CEUS parameters that may best predict disease still warrant systematic evaluation, animal models and limited clinical trials in humans raise hopes that CEUS could outcompete competing modalities as a first-line tool for assessing renal perfusion non-invasively, even in ailments such as acute kidney injury and chronic kidney disease. PMID:28191530
Mathew-Steiner, Shomita S.; Dixith, Sriteja; Vanzant, Daniel; Kim, Jayne; Dickerson, Jennifer L.; Datta, Soma; Powell, Heather; Roy, Sashwati; Bergdall, Valerie; Sen, Chandan K.
This work represents the first study employing non-invasive high-resolution harmonic ultrasound imaging to longitudinally characterize skin wound healing. Burn wounds (day 0-42), on the dorsum of a domestic Yorkshire white pig were studied non-invasively using tandem digital planimetry, laser speckle imaging and dual mode (B and Doppler) ultrasound imaging. Wound depth, as measured by B-mode imaging, progressively increased until day 21 and decreased thereafter. Initially, blood flow at the wound edge increased up to day 14 and subsequently regressed to baseline levels by day 21, when the wound was more than 90% closed. Coinciding with regression of blood flow at the wound edge, there was an increase in blood flow in the wound bed. This was observed to regress by day 42. Such changes in wound angiogenesis were corroborated histologically. Gated Doppler imaging quantitated the pulse pressure of the primary feeder artery supplying the wound site. This pulse pressure markedly increased with a bimodal pattern following wounding connecting it to the induction of wound angiogenesis. Finally, ultrasound elastography measured tissue stiffness and visualized growth of new tissue over time. These studies have elegantly captured the physiological sequence of events during the process of wound healing, much of which is anticipated based on certain dynamics in play, to provide the framework for future studies on molecular mechanisms driving these processes. We conclude that the tandem use of non-invasive imaging technologies has the power to provide unprecedented insight into the dynamics of the healing skin tissue. PMID:25799513
Lin, Pei-Yi; Roche-Labarbe, Nadege; Dehaes, Mathieu; Carp, Stefan; Fenoglio, Angela; Barbieri, Beniamino; Hagan, Katherine; Grant, P Ellen; Franceschini, Maria Angela
Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO₂). Thus, measures of CMRO₂ are reflective of neuronal viability and provide critical diagnostic information, making CMRO₂ an ideal target for bedside measurement of brain health. Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases. Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO₂) as a surrogate for cerebral oxygen consumption. However, SO₂ is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO₂ are not sensitive enough to detect brain injury hours after the insult, because oxygen consumption and delivery reach equilibrium after acute transients. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO₂ (CMRO₂i). With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain
Zhang, Xi; Owens, Gabe E.; Gurm, Hitinder S.; Ding, Yu; Cain, Charles A.; Xu, Zhen
Histotripsy has been investigated as a non-invasive, drug-free, image-guided thrombolysis method that fractionates blood clots using acoustic cavitation alone. In previous histotripsy-mediated thrombolysis studies, cavitation clouds were generated using multi-cycle pulses and tended to form on vessel wall. To avoid potential cavitational damage to vessel wall, a new histotripsy approach, termed Microtripsy, has been recently discovered where cavitation is generated via an intrinsic-threshold mechanism using single-cycle pulses. We hypothesize that microtripsy can generate and confine cavitation in vessel lumen without contacting vessel wall, which results in recanalization within clot and potentially eliminating vessel damage. To test our hypothesis, microtripsy was investigated for clot recanalization in an in vitro flow model. Clots were formed inside a vessel phantom (6.5 mm inner diameter) in line with a flow system. Microtripsy was applied by a 1-MHz transducer at a pulse repetition frequency of 50 Hz with a peak negative pressure (P-) of 30 MPa or 36 MPa. To create a flow channel through a clot, the cavitation focus was scanned through the clot at an interval of 0.3 or 0.7 mm. The treated clots were 3D-scanned by a 20-MHz ultrasound probe to quantify the channels. Restored flow rates were measured and clot debris particles generated from the treatments were analyzed. In all treatments, cavitation cloud was consistently generated in the center of the vessel lumen without contacting the vessel wall. After each treatment, a flow channel was successfully generated through and completely confined inside the clot. The channels had a diameter up to 60 % of the vessel diameter with restored flow up to 500 mL/min. The debris particles were small with over 99.9% < 10 μm and the largest at 153 um. Each clot (2 cm long) was recanalized within 7 min. The size of the flow channels increased by using higher P- and was significantly larger by using the 0.3 mm scan interval
Moretti, M.; Cilione, C.; Tampieri, A.; Fracchia, C.; Marchioni, A.; Nava, S.
BACKGROUND—The rate of failure of non-invasive mechanical ventilation (NIMV) in patients with chronic obstructive pulmonary disease (COPD) with acute respiratory insufficiency ranges from 5% to 40%. Most of the studies report an incidence of "late failure" (after >48 hours of NIMV) of about 10-20%. The recognition of this subset of patients is critical because prolonged application of NIMV may unduly delay the time of intubation. METHODS—In this multicentre study the primary aims were to assess the rate of "late NIMV failure" and possible associated predictive factors; secondary aims of the study were evaluation of the best ventilatory strategy in this subset of patients and their outcomes in and out of hospital. The study was performed in two respiratory intensive care units (ICUs) on patients with COPD admitted with an episode of hypercapnic respiratory failure (mean (SD) pH 7.23(0.07), PaCO2 85.3 (15.8) mm Hg). RESULTS—One hundred and thirty seven patients initially responded to NIMV in terms of objective (arterial blood gas tensions) and subjective improvement. After 8.4 (2.8) days of NIMV 31 patients (23%; 95% confidence interval (CI) 18 to 33) experienced a new episode of acute respiratory failure while still ventilated. The occurrence of "late NIMV failure" was significantly associated with functional limitations (ADL scale) before admission to the respiratory ICU, the presence of medical complications (particularly hyperglycaemia), and a lower pH on admission. Depending on their willingness or not to be intubated, the patients received invasive ventilation (n=19) or "more aggressive" (more hours/day) NIMV (n=12). Eleven (92%) of those in this latter subgroup died while in the respiratory ICU compared with 10 (53%) of the patients receiving invasive ventilation. The overall 90 day mortality was 21% and, after discharge from hospital, was similar in the "late NIMV failure" group and in patients who did not experience a second episode of acute
Kovacs, Gabor; Avian, Alexander; Foris, Vasile; Tscherner, Maria; Kqiku, Xhylsime; Douschan, Philipp; Bachmaier, Gerhard; Olschewski, Andrea; Matucci-Cerinic, Marco; Olschewski, Horst
Background There is a broad consensus that pulmonary hypertension (PH) is to be diagnosed by right heart catheterization (RHC) and that the most important non-invasive tool is echocardiography. However, the role of simple non-invasive tools in the work-up of PH is not clearly defined. We hypothesized that the use of simple non-invasive techniques may help to guide important decisions in the diagnostics of pulmonary hypertension. Objectives We aimed to develop an algorithm with the use of simple, non-invasive tools in order to identify patients with very high or very low likelihood of PH. Methods We retrospectively analyzed all consecutive patients undergoing RHC between 2005 and 2010 in our center and performed logistic regression of simple non-invasive parameters regarding detection and exclusion of PH and derived a two-step algorithm. In a prospective study we evaluated this algorithm between 2011 and 2013. Results The retrospective cohort consisted of n = 394 patients of which 49% presented with PH. Right axis deviation in the ECG was present in 90/394 patients and had a positive predictive value (PPV) of 93% for PH. The combination of non-right axis deviation, N-terminal pro brain natriuretic peptide (NT-proBNP)<333pg/ml, arterial oxygen saturation (SO2)≥95.5% and WHO functional class I-II was present in 69/394 patients and excluded PH with a negative predictive value (NPV) of 96%. The prospective study confirmed these results in a cohort of n = 168 patients (PPV:92%, NPV:97%). Taken together, simple non-invasive tools allowed a prediction regarding the presence or absence of PH in 42% of patients with suspected PH. Conclusion ECG, NT-proBNP, SO2 and WHO functional class may predict the presence or absence of PH in almost half of the patients with suspected PH, suggesting an important role for these variables in the work-up of patients at risk for PH. Clinical Trial Registration NCT01607502 PMID:28030578
frequency range of 15 to 150 kHz. Currents in this frequency range will not effectively stimulate the heart or skeletal muscle. The output of the bridge is...input impedance instrumentation amplifier. This stage does not load the bridge, i.e. draw current , and eliminates unwanted noise signals common to the...ground loops will be effectively eliminated. The currently used ±9 volt supply (12 "C" batteries) will power the back end (i.e. the processing circuitry
Maina, John N; Jimoh, Sikiru A
Complete blood-gas barrier breaks (BGBBs) and epithelial-epithelial cells connections breaks (E-ECCBs) were enumerated in the lungs of free range chickens, Gallus gallus variant domesticus after vascular perfusion at different pressures. The E-ECCBs surpassed the BGBBs by a factor of ~2. This showed that the former parts of the gas exchange tissue were structurally weaker or more vulnerable to failure than the latter. The differences in the numbers of BGBBs and E-ECCBs in the different regions of the lung supplied with blood by the 4 main branches of the pulmonary artery (PA) corresponded with the diameters of the blood vessels, the angles at which they bifurcated from the PA, and the positions along the PA where they branched off. Most of the BGBBs and the E-ECCBs occurred in the regions supplied by the accessory- and the caudomedial branches: the former is the narrowest branch and the first blood vessel to separate from the PA while the latter is the most direct extension of the PA and is the widest. The E-ECCBs appeared to separate and fail from tensing of the blood capillary walls, as the perfusion- and intramural pressures increased. Compared to the mammalian lungs on which data are available, i.e., those of the rabbit, the dog, and the horse, the blood-gas barrier of the lung of free range chickens appears to be substantially stronger for its thinness. PMID:25288905
Nitzan, Meir; Nitzan, Itamar
The oxygen saturation of the systemic arterial blood is associated with the adequacy of respiration, and can be measured non-invasively by pulse oximetry in the systemic tissue. The oxygen saturation of the blood in the pulmonary artery, the mixed venous blood, reflects the balance between oxygen supply to the systemic tissues and their oxygen demand. The mixed venous oxygen saturation has also clinical significance because it is used in Fick equation for the quantitative measurement of cardiac output. At present the measurement of the mixed venous oxygen saturation is invasive and requires insertion of a Swan-Ganz catheter into the pulmonary artery. We suggest a noninvasive method for the measurement of the mixed venous oxygen saturation in infants, pulmonary pulse oximetry. The method is similar to the systemic pulse oximetry, which is based on the different light absorption curves of oxygenated and deoxygenated hemoglobin and on the analysis of photoplethysmographic curves in two wavelengths. The proposed pulmonary pulse oximeter includes light-sources of two wavelengths in the infrared, which illuminate the pulmonary tissue through the thoracic wall. Part of the light which is scattered back from the pulmonary tissue and passes through the thoracic wall is detected, and for each wavelength a pulmonary photoplethysmographic curve is obtained. The pulmonary photoplethysmographic curves reflect blood volume increase during systole in the pulmonary arteries in the lung tissue, which contain mixed venous blood. The ratio R of the amplitude-to-baseline ratio for the two wavelengths is related to the mixed venous oxygen saturation through equations derived for the systemic pulse oximetry. The method requires the use of extinction coefficients values for oxygenated and deoxygenated hemoglobin, which can be found in the literature.
Timchalk, Chuck; Campbell, James A.; Liu, Guodong; Lin, Yuehe; Kousba, Ahmed A.
Abstract Non-invasive biomonitoring approaches are being developed using reliable portable analytical systems to quantify dosimetry utilizing readily obtainable body fluids, such as saliva. In the current study, rats were given single oral gavage doses (1, 10 or 50 mg/kg) of the insecticide chlorpyrifos (CPF), saliva and blood were collected from groups of animals (4/time-point) at 3, 6, and 12 hr post-dosing, and the samples were analyzed for the CPF metabolite trichlorpyridinol (TCP). Trichlorpyridinol was detected in both blood and saliva at all doses and the TCP concentration in blood exceeded saliva, although the kinetics in blood and saliva were comparable. A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF incorporated a compartment model to describe the time-course of TCP in blood and saliva. The model adequately simulated the experimental results over the dose ranges evaluated. A rapid and sensitive sequential injection (SI) electrochemical immunoassay was developed to monitor TCP, and the reported detection limit for TCP in water was 6 ng/L. Computer model simulation in the range of the Allowable Daily Intake (ADI) or Reference Dose (RfD) for CPF (0.01-0.003 mg/kg/day) suggest that the electrochemical immunoassay had adequate sensitivity to detect and quantify TCP in saliva at these low exposure levels. To validate this approach further studies are needed to more fully understand the pharmacokinetics of CPF and TCP excretion in saliva. The utilization of saliva as a biomonitoring matrix, coupled to real-time quantitation and PBPK/PD modeling represents a novel approach with broad application for evaluating both occupational and environmental exposures to insecticides.
Hussein, Hassan A
placentomal blood perfusion. In conclusion, depicting blood flow within the middle uterine artery using color Doppler sonography could be helpful in correct diagnosis of duration and degree of uterine torsion and concurrently predicting the viability of the fetus and dam.
de Carvalho Ferreira, H C; Weesendorp, E; Quak, S; Stegeman, J A; Loeffen, W L A
A challenging aspect of ASFV control in wild boar populations is the design and implementation of effective surveillance and monitoring programmes, both for early warning, and to determine the ongoing epidemiological situation in an infected population. Testing blood samples requires invasive sampling strategies like hunting or capture of wild boar. Besides being biased towards healthy animals, such strategies are also linked to further spread of the virus. Non-invasive sampling strategies would increase the reliability of surveillance of ASFV in wild boar populations, without the negative side effects. This study evaluates the potential of faeces and tissue samples as a basis for non-invasive sampling strategies for ASFV in wild boar. In the acute phase (0-21 days after infection), in comparison with virus detection in blood, virus can be detected in faeces 50-80% of the time. This percentage decreases to below 10% for the subacute/chronic phase. ASFV DNA is quite stable in faeces. Half-lives range from more than 2 years at temperature up to 12°C, to roughly 15 days at temperatures of 30°C. In tissue samples, stored at 20°C, half-lives mostly range from 1.7 to 7.4 days. The sample of preference is the spleen, where the highest titres and highest half-life of ASFV DNA are observed. The level and duration of excretion of ASFV in the faeces, combined with the stability of the DNA, suggest that sampling of faeces could be the basis for a non-invasive sampling strategy to monitor ASFV in wild boar.
Rivara, Claire B; Chevrolet, Jean-Claude; Gasche, Yvan; Charbonney, Emmanuel
Gas embolism is a dreaded complication following invasive medical procedures, traumatic lung injury and decompression accidents. We report a case of fatal gas embolism following the use of non-invasive ventilation (NIV) with bilevel positive airway pressure (BiPAP). The patient initially underwent left bronchial artery embolisation for massive haemoptysis in the context of severe tuberculotic sequels. Under NIV and after heavy coughing he became hemiparetic and his level of consciousness suddenly dropped. Computed tomography of the brain showed multiple air embolism and ischaemic lesions were confirmed by magnetic resonance imaging. Echocardiographic investigations showed no intracardiac defect. Vasculo-pulmonary abnormalities in the context of heavy coughing and non-invasive ventilation may have played a major role in the occurrence of this event. New neurological events in a patient with tuberculotic sequels or any known vascular pulmonary abnormalities and NIV should raise the suspicion of brain gas embolism. PMID:21716825
Uhlig, Tino; Wiedwald, Ulf; Seidenstücker, Axel; Ziemann, Paul; Eng, Lukas M
We present an easy, fast and reliable method for the preparation of magnetic force microscopy (MFM) probes based on single Co nanoparticles (NPs). Due to their dipolar character, these magnetic probes open up a new approach for quantitative and non-invasive MFM measurements on the nanometer length scale. To guarantee long-term stability of these tips under ambient conditions, an ultrathin protecting Au shell was grown around the Co NPs through photochemical deposition. Single magnetic particles were firmly attached to standard silicon AFM tips using bifunctional self-assembling molecules. Such probes were tested on longitudinal magnetic recording media and compared to the results as recorded with conventional thin-film MFM tips. Easy data interpretation of the magnetic nanoparticle probes in a point dipole model is shown. Our nanoparticle tips provide excellent endurance for MFM recording, enable non-invasive probing while maintaining a high sensitivity, resolution, and reproducibility.
Yue, Kun; Guduru, Rakesh; Hong, Jeongmin; Liang, Ping; Nair, Madhavan; Khizroev, Sakhrat
This paper for the first time discusses a computational study of using magneto-electric (ME) nanoparticles to artificially stimulate the neural activity deep in the brain. The new technology provides a unique way to couple electric signals in the neural network to the magnetic dipoles in the nanoparticles with the purpose to enable a non-invasive approach. Simulations of the effect of ME nanoparticles for non-invasively stimulating the brain of a patient with Parkinson's Disease to bring the pulsed sequences of the electric field to the levels comparable to those of healthy people show that the optimized values for the concentration of the 20-nm nanoparticles (with the magneto-electric (ME) coefficient of 100 V cm−1 Oe−1 in the aqueous solution) is 3×106 particles/cc, and the frequency of the externally applied 300-Oe magnetic field is 80 Hz. PMID:22957042
Sennerby, L; Wennerberg, A; Pasop, F
A new X-ray microtomographic technique for non-invasive assessment of the structure of bone surrounding implants was tested. Three titanium microimplants retrieved directly (n = 2) or 6 months (n = 1) after insertion in 3 patients were used as test samples. Two samples were used dry and one was embedded in plastic resin prior to microtomography. The technique provided high-resolution consecutive cross-sectional X-ray images of the specimens with a slice-to-slice distance of 4.4 to 11.0 microns. The pictures could be imported into an image analysing software with which semiautomatic quantitative measurement of the bone area and three-dimensional images of the specimens could be made. It is suggested that the technique may be used for non-invasive assessment of the bone structure around implants. Further studies are needed to evaluate the accuracy of the technique, for instance by comparing tomographic sections with histologic ones.
Mukherjee, Arnab; Wu, Di; Davis, Hunter C.; Shapiro, Mikhail G.
Non-invasive imaging of gene expression in live, optically opaque animals is important for multiple applications, including monitoring of genetic circuits and tracking of cell-based therapeutics. Magnetic resonance imaging (MRI) could enable such monitoring with high spatiotemporal resolution. However, existing MRI reporter genes based on metalloproteins or chemical exchange probes are limited by their reliance on metals or relatively low sensitivity. Here we introduce a new class of MRI reporters based on the human water channel aquaporin 1. We show that aquaporin overexpression produces contrast in diffusion-weighted MRI by increasing tissue water diffusivity without affecting viability. Low aquaporin levels or mixed populations comprising as few as 10% aquaporin-expressing cells are sufficient to produce MRI contrast. We characterize this new contrast mechanism through experiments and simulations, and demonstrate its utility in vivo by imaging gene expression in tumours. Our results establish an alternative class of sensitive, metal-free reporter genes for non-invasive imaging.
Greene, R M; Saleh, A; Taylor, A K; Callaghan, M; Addis, B J; Nzewi, O C; van Zyl, W V
Because of its ability to depict intravascular, intramural, and extramural pathology, non-invasive imaging is well suited to assessing life-threatening hemoptysis that may complicate Behçet disease. We made exclusive use of CT angiography supplemented by MR to identify pulmonary thromboembolism, mediastinal lymphadenopathy, and bilateral pulmonary artery aneurysms with signs of previous unilateral rupture. Two-dimensional reformatted CT images provided surgeons with a road map of upstream and downstream vascular relationships prior to aneurysm resection. Imaging findings were confirmed by surgery and pathology. Non-invasive imaging proved to be a useful alternative to standard catheter arteriography in the preoperative assessment of hemoptysis in this patient with Behçet disease.
Engelmann, Guido; Quader, Jasmin; Teufel, Ulrike; Schenk, Jens Peter
Changes in liver structure are an important issue in chronic hepatopathies. Until the end of the 20th century, these changes could only be determined by histological analyses of a liver specimen obtained via biopsy. The well-known limitations of this technique (i.e., pain, bleeding and the need for sedation) have precluded its routine use in follow-up of patients with liver diseases. However, the introduction of non-invasive technologies, such as ultrasound and magnetic resonance imaging, for measurement of liver stiffness as an indirect marker of fibroses has changed this situation. Today, several non-invasive tools are available to physicians to estimate the degree of liver fibrosis by analysing liver stiffness. This review describes the currently available tools for liver stiffness determination that are applicable to follow-up of liver fibrosis/cirrhosis with established clinical use in children, and discusses their features in comparison to the “historical” tools. PMID:28357028
Ramamonjisoa, Nirilanto; Ackerstaff, Ellen
Tumors are often characterized by hypoxia, vascular abnormalities, low extracellular pH, increased interstitial fluid pressure, altered choline-phospholipid metabolism, and aerobic glycolysis (Warburg effect). The impact of these tumor characteristics has been investigated extensively in the context of tumor development, progression, and treatment response, resulting in a number of non-invasive imaging biomarkers. More recent evidence suggests that cancer cells undergo metabolic reprograming, beyond aerobic glycolysis, in the course of tumor development and progression. The resulting altered metabolic content in tumors has the ability to affect cell signaling and block cellular differentiation. Additional emerging evidence reveals that the interaction between tumor and stroma cells can alter tumor metabolism (leading to metabolic reprograming) as well as tumor growth and vascular features. This review will summarize previous and current preclinical, non-invasive, multimodal imaging efforts to characterize the tumor microenvironment, including its stromal components and understand tumor–stroma interaction in cancer development, progression, and treatment response. PMID:28197395
Flamini, Vittoria; Creane, Arthur P; Kerskens, Christian M; Lally, Caitríona
Characterization of the mechanical properties of arterial tissues usually involves an invasive procedure requiring tissue removal. In this work we propose a non-invasive method to perform a biomechanical analysis of cardiovascular aortic tissue. This method is based on combining medical imaging and finite element analysis (FEA). Magnetic resonance imaging (MRI) was chosen since it presents relatively low risks for human health. A finite element model was created from the MRI images and loaded with systolic physiological pressures. By means of an optimization routine, the structural material properties were changed until average strains matched those measured by MRI. The method outlined in this work produced an estimate of the in situ properties of cardiovascular tissue based on non-invasive image datasets and finite element analysis.
Nagashima, Saki; Sakurai, Kenichi; Suzuki, Shuhei; Hara, Yukiko; Maeda, Tetsuyo; Hirano, Tomohisa; Enomoto, Katsuhisa; Amano, Sadao; Koshinaga, Tsugumichi
CD147 is a multifunctional membrane glycoprotein involved in tumor invasion, and is overexpressed in many solid tumors. However, the role of CD147 in breast cancer is not well understood. The aim of this study was to evaluate CD147 expression in non-invasive and invasive ductal carcinomas. We recruited 156 breast cancer patients who underwent radical operations at our hospital up until 2002. We performed immunohistochemistry on their tumor specimens, and compared these data with clinicopathological factors. We divided the patients into two groups: group A was comprised of non-invasive ductal carcinomas and group B, invasive ductal carcinomas. The CD147-positive rate was 62.8% for all patients and was higher in group B than group A. In all cases, the CD147-positive rate correlated with clinical stage, number of metastatic lymph nodes, and tumor size. These results implied that CD147 may be involved in the process of breast cancer invasion.
Miliani, C.; Rosi, F.; Daveri, A.; Brunetti, B. G.
The potential of fibre optic reflection infrared spectroscopy for the non-invasive identification of artists' pigments is presented. Sixteen different carbonate, sulphate and silicate-based pigments are taken into account considering their wide use during the history of art and their infrared optical properties. The infrared distortions mainly generated by the specular reflection are discussed on the basis of experimental measurements carried out on reference samples. The study on pure materials permitted the definition of marker bands, mainly combination and overtone modes, enhanced by the diffuse reflection component of the light, functional for the non-invasive pigment identification in real artworks. Several case studies are reported, including wall, easel, canvas paintings and manuscripts from ancient to modern art demonstrating the strengths of the technique on the identification of pigments even in the presence of complex mixtures of both organic (binders, varnishes) and inorganic (supports, fillers and other pigments) compounds.
Koski, Kristie J.; Akhenblit, Paul; McKiernan, Keri; Yarger, Jeffery L.
Spider silks possess nature’s most exceptional mechanical properties, with unrivalled extensibility and high tensile strength. Unfortunately, our understanding of silks is limited because the complete elastic response has never been measured—leaving a stark lack of essential fundamental information. Using non-invasive, non-destructive Brillouin light scattering, we obtain the entire stiffness tensors (revealing negative Poisson’s ratios), refractive indices, and longitudinal and transverse sound velocities for major and minor ampullate spider silks: Argiope aurantia, Latrodectus hesperus, Nephila clavipes, Peucetia viridans. These results completely quantify the linear elastic response for all possible deformation modes, information unobtainable with traditional stress-strain tests. For completeness, we apply the principles of Brillouin imaging to spatially map the elastic stiffnesses on a spider web without deforming or disrupting the web in a non-invasive, non-contact measurement, finding variation among discrete fibres, junctions and glue spots. Finally, we provide the stiffness changes that occur with supercontraction.
Parkin, Beth L; Ekhtiari, Hamed; Walsh, Vincent F
The use of non-invasive brain stimulation is widespread in studies of human cognitive neuroscience. This has led to some genuine advances in understanding perception and cognition, and has raised some hopes of applying the knowledge in clinical contexts. There are now several forms of stimulation, the ability to combine these with other methods, and ethical questions that are special to brain stimulation. In this Primer, we aim to give the users of these methods a starting point and perspective from which to view the key questions and usefulness of the different forms of non-invasive brain stimulation. We have done so by taking a critical view of recent highlights in the literature, selected case studies to illustrate the elements necessary and sufficient for good experiments, and pointed to questions and findings that can only be addressed using interference methods.
Herring, Rodney A; Jacquemin, Peter; Sawicka, Barbara D; Atalick, Stefan
A confocal acoustic holography microscope (CAHM) has been designed, simulated and partially verified experimentally to take holograms for non-invasive, three-dimensional measurements of a specimen's refractive indices from one view point. The designed and simulated prototype CAHM used a frequency of 2.25 MHz and measured sound speed changes of 16 m/s, temperature changes of 5 degrees C and had a spatial resolution of 660 microm. With future improvements utilizing the latest technologies such as two-dimensional array detectors, Micro-Electro-Mechanical Systems (MEMS), and acoustic lenses, resolutions of 1m/s, 0.5 degrees C, and 150 microm are expected. The CAHM is expected to have many useful applications, including non-invasive mass and heat transfer measurements in fluids and materials and as a medical diagnostic tool to non-intrusively visualize compositions and temperatures within the human body.
Walsh, I K; Thompson, T; Loughridge, W G; Johnston, S R; Keane, P F; Stone, A R
Patients with intractably diminished bladder storage function are encountered frequently by neurourologists, occasionally requiring reconstructive surgery for appropriate resolution. Although sacral neuromodulation is a recognized effective therapeutic modality, present techniques are technically demanding, invasive, and expensive. This study investigated the effect of non-invasive third sacral nerve (S3) stimulation on bladder activity during filling cystometry. One hundred forty-six patients underwent standard urodynamic filling cystometry that was then immediately repeated. Patients in the study group (n = 74) received antidromic transcutaneous sacral neurostimulation during the second fill and the control group (n = 72) underwent a second fill without neurostimulation. A statistically significant increase in bladder storage capacity without a corresponding rise in detrusor pressure was observed in the neurostimulated patients. This improvement in functional capacity is an encouraging finding that further supports the use of this non-invasive treatment modality in clinical practice.
Non-invasive transcranial high intensity focused ultrasound (HIFUS) therapy given under MRI thermometry and image guidance to awake patients lying within the bore of a 1.5 T MRI scanner (a) to thermally ablate brain lesions such as metastases, (b) to cause precise ablative brain lesions in functional disorders, or (c) to locally open the blood-brain-barrier for targeted therapeutic construct delivery--without the radiation risks of stereotactic radiotherapy--may sound science fiction. Kullervo Hynynen, a Finnish-born ultrasound and MRI physicist, and Ferenc Jolesz, a Hungarian-born neurosurgeon and visionary of image guided surgery, have joined forces at Radiology, Brigham & Women's Hospital, Boston, and they have taken every step to realize the vision above, in highly successful collaboration with the industry (GE, InSightec, TxSonics). The sophisticated transcranial HIFUS instrumentation, supported by profound research data from experimental animals and by the clinical experience from extracranial HIFUS targets (breast fibroadenoma, uterine fibroid), is now coming to a phase I clinical trial in cerebral metastases. It remains to be seen whether transcranial HIFUS will find applications in diffuse gliomas such as (a) thermal ablation of selected areas of glioma tissue, (b) opening the blood-brain-barrier for therapeutic constructs to enter selected areas, or (c) activating such constructs in desired areas. The prophecy of Dr. Jolesz, "this technology will put neurosurgeons out of business", may not fulfill during our lifetime.
Hill, Melissa; Compton, Cecilia; Karunaratna, Madhavi; Lewis, Celine; Chitty, Lyn
In the near future the availability of non-invasive prenatal diagnosis (NIPD) for single gene disorders will change the prenatal diagnosis options available to couples who are carriers of conditions such as cystic fibrosis, sickle cell disorder and thalassaemia. Client opinions about NIPD are needed to inform the implementation of NIPD for single gene disorders. This qualitative study used two focus groups (n = 12) and one-to-one interviews (n = 16) with carriers and support group representatives of sickle cell disease, thalassaemia and cystic fibrosis. Discussions were digitally recorded, transcribed verbatim and analysed using thematic analysis. Opinions about NIPD were very positive and participants valued the opportunity to have safe and early testing. Uptake of prenatal testing is likely to increase as women who had previously declined invasive testing expressed interest in having NIPD. Participant concerns about NIPD centred on the need for accuracy to be high to be used for subsequent decision making about termination of pregnancy. Participants also raised concerns that less thought may be given to having a blood test compared to an invasive test and that the perceived ease of a blood test may bring increased pressure to have testing. Participants thought NIPD should be offered through existing specialist services to ensure appropriate genetic counseling and support. Maintaining all testing options is important as some people may prefer invasive testing over NIPD if invasive testing was more accurate or if invasive testing could give information about other conditions such as Down syndrome.
Ukawa, Teiji; Takayanagi, Tsuneo; Morimoto, Haruka; Higashi, Yukihito; Idei, Naomi; Yoshizumi, Masao; Tsuji, Toshio
Measurement of flow-mediated dilatation (FMD) is the conventional non-invasive method for assessment of endothelial function; however, it requires an expensive ultrasound system and high levels of technical skill. Therefore, we developed a novel method for measurement of endothelial function, namely, measurement of ezFMD. ezFMD estimates the degree of vasodilatation from the oscillation signals transmitted to a sphygmomanometer cuff attached to the upper arm. The objective of this study was to validate the principle underlying the measurement of ezFMD, and to evaluate the repeatability of the ezFMD measurements. We observed the blood vessel behavior and oscillometric pattern in ten subjects. When the cuff was inflated to the level of the mean blood pressure, the oscillation amplitude increased with increasing degree of vasodilatation. In experiment to evaluate the repeatability of the ezFMD measurement, the average difference between the paired measurements was 3.7 %, the standard deviation was 11.5 %, and the average coefficient of variation value for the 11 paired measurements was 23.7 %. These results suggest the validity of the principle underlying the measurement of the ezFMD for the assessment of endothelial function. And, this study suggests that the repeatability of the ezFMD measurements is superior to that of the conventional measurement of FMD.
Wang, Ming-Jun; Ling, Wen-Wu; Wang, Hong; Meng, Ling-Wei; Cai, He; Peng, Bing
AIM To investigate the diagnostic performance of liver stiffness measurement (LSM) by elastography point quantification (ElastPQ) in animal models and determine the longitudinal changes in liver stiffness by ElastPQ after splenectomy at different stages of fibrosis. METHODS Liver stiffness was measured in sixty-eight rabbits with CCl4-induced liver fibrosis at different stages and eight healthy control rabbits by ElastPQ. Liver biopsies and blood samples were obtained at scheduled time points to assess liver function and degree of fibrosis. Thirty-one rabbits with complete data that underwent splenectomy at different stages of liver fibrosis were then included for dynamic monitoring of changes in liver stiffness by ElastPQ and liver function according to blood tests. RESULTS LSM by ElastPQ was significantly correlated with histologic fibrosis stage (r = 0.85, P < 0.001). The optimal cutoff values by ElastPQ were 11.27, 14.89, and 18.21 kPa for predicting minimal fibrosis, moderate fibrosis, and cirrhosis, respectively. Longitudinal monitoring of the changes in liver stiffness by ElastPQ showed that early splenectomy (especially F1) may delay liver fibrosis progression. CONCLUSION ElastPQ is an available, convenient, objective and non-invasive technique for assessing liver stiffness in rabbits with CCl4-induced liver fibrosis. In addition, liver stiffness measurements using ElastPQ can dynamically monitor the changes in liver stiffness in rabbit models, and in patients, after splenectomy. PMID:28028365
Amemori, Satoko; Amemori, Ken-ichi; Cantor, Margaret L.; Graybiel, Ann M.
Background We have developed a novel head-holding device for behaving non-human primates that affords stability suitable for reliable chronic electrophysiological recording experiments. The device is completely non-invasive, and thus avoids the risk of infection and other complications that can occur with the use of conventional, surgically implanted head-fixation devices. New method The device consists of a novel non-invasive head mold and bar clamp holder, and is customized to the shape of each monkey’s head. The head-holding device that we introduce, combined with our recording system and reflection-based eye-tracking system, allows for chronic behavioral experiments and single-electrode or multi-electrode recording, as well as manipulation of brain activity. Results and comparison with existing methods With electrodes implanted chronically in multiple brain regions, we could record neural activity from cortical and subcortical structures with stability equal to that recorded with conventional head-post fixation. Consistent with the non-invasive nature of the device, we could record neural signals for more than two years with a single implant. Importantly, the monkeys were able to hold stable eye fixation positions while held by this device, demonstrating the possibility of analyzing eye movement data with only the gentle restraint imposed by the non-invasive head-holding device. Conclusions We show that the head-holding device introduced here can be extended to the head holding of smaller animals, and note that it could readily be adapted for magnetic resonance brain imaging over extended periods of time. PMID:25448381
Gall, Carolin; Silvennoinen, Katri; Granata, Giuseppe; de Rossi, Francesca; Vecchio, Fabrizio; Brösel, Doreen; Bola, Michał; Sailer, Michael; Waleszczyk, Wioletta J; Rossini, Paolo M; Tatlisumak, Turgut; Sabel, Bernhard A
Occipital stroke often leads to visual field loss, for which no effective treatment exists. Little is known about the potential of non-invasive electric current stimulation to ameliorate visual functions in patients suffering from unilateral occipital stroke. One reason is the traditional thinking that visual field loss after brain lesions is permanent. Since evidence is available documenting vision restoration by means of vision training or non-invasive electric current stimulation future studies should also consider investigating recovery processes after visual cortical strokes. Here, protocols of repetitive transorbital alternating current stimulation (rtACS) and transcranial direct current stimulation (tDCS) are presented and the European consortium for restoration of vision (REVIS) is introduced. Within the consortium different stimulation approaches will be applied to patients with unilateral occipital strokes resulting in homonymous hemianopic visual field defects. The aim of the study is to evaluate effects of current stimulation of the brain on vision parameters, vision-related qu