Estimation Of Blood Flow Research Articles

Cerebral Blood Flow and Aβ-Amyloid Estimates by WARM Analysis of [11C]PiB Uptake Distinguish among and between Neurodegenerative Disorders and Aging.

Background: We report results of the novel Washout Allometric Reference Method (WARM) that uses estimates of cerebral blood flow and amyloid load from the same [11C]Pittsburgh Compound B ([11C]PiB) retention maps in brain to distinguish between patients with different forms dementia, including Alzheimer’s disease, and healthy volunteers. The method introduces two approaches to the identification of brain pathology related to amyloid accumulation, (1) a novel analysis of amyloid binding based on the late washout of the tracer from brain tissue, and (2) the simultaneous estimation of absolute cerebral blood flow indices (sCBF) from the early accumulation of the tracer in brain tissue.Objective: We tested the hypothesis that a change of cerebral blood flow is correlated with the degree of tracer [11C]PiB retention, reflecting dendritic spine pathology and consequent inhibition of brain energy metabolism and reduction of blood flow by neurovascular coupling in neurodegenerative disorders, including Alzheimer’s disease.Methods: Previously reported images of [11C]PiB retention in brain of 29 subjects with cognitive impairment or dementia [16 Alzheimer’s Disease (AD), eight subjects with dementia with Lewy bodies (DLB), five patients with frontotemporal lobar degeneration (FTLD), five patients with mild cognitive impairment, and 29 age-matched healthy control subjects (HC)], underwent analysis of PiB delivery and retention by means of WARM for quantitation of [11C]PiB’s binding potentials (BPND) and correlated surrogate cerebral blood flow (sCBF) estimates, based on the [11C]PiB images, compared to estimates by conventional Standard Uptake Value Ratio (SUVR) of [11C]PiB retention with cerebellum gray matter as reference. Receiver Operating Characteristics (ROC) revealed the power of discrimination among estimates.Results: For AD, the discriminatory power of [11C]PiB binding potential (BPND) by WARM exceeded the power of SUVR that in turn exceeded the power of sCBF estimates. Differences of [11C]PiB binding and sCBF measures between AD and HC both were highly significant (p < 0.001). For all the dementia groups as a whole, sCBF estimates revealed the greatest discrimination between the patient and HC groups. WARM resolves a major issue of amyloid load quantification with [11C]PiB in human brain by determining absolute sCBF and amyloid load measures from the same images. The two parameter approach provides key discriminary information in AD for which [11C]PiB traditionally is used, as well as for the distinct flow deficits in FTLD, and the marked parietal and occipital lobe flow deficits in DLB.Conclusion: We conclude that WARM yields estimates of two important variables that together discriminate among patients with dementia, including AD, and healthy volunteers, with ROC that are superior to conventional methods of analysis. The distinction between estimates of flow and amyloid load from the same dynamic emission tomograms provides valuable pathogenetic information.

Estimation of Blood Flow and Wall Shear Stress after Aortic Dissection by CFD

Estimation of Blood Flow and Wall Shear Stress after Aortic Dissection by CFD

THE METHOD OF ULTRASONIC EVALUATION OF THE UTERUS

The article includes basic rules of conducting ultrasound examination of the uterine appendages: the ovaries and fallopian tubes. The dynamics of changes in the internal structure of the ovaries in relation to the phases menstrual cycle, ovarian blood flow and the possibility of estimating blood flow parameters are discussed.

Improving the estimation of flow speed for laser speckle imaging with single exposure time

Laser speckle contrast imaging is a full-field imaging technique for measuring blood flow by mapping the speckle contrast with high spatial and temporal resolution. However, the statically scattered light from stationary tissues seriously degrades the accuracy of flow speed estimation. In this Letter, we present a simple calibration approach to calculate the proportions of dynamically scattered light and correct the effect of static scattering with single exposure time. Both the phantom and animal experimental results suggest that this calibration approach has the ability to improve the estimation of the relative blood flow in the presence of static scattering.

In Vivo Validation of Volume Flow Measurements of Pulsatile Flow Using a Clinical Ultrasound System and Matrix Array Transducer

The goal of this study was to evaluate the accuracy of a non-invasive C-plane Doppler estimation of pulsatile blood flow in the lower abdominal vessels of a porcine model. Doppler ultrasound measurements from a matrix array transducer system were compared with invasive volume flow measurements made on the same vessels with a surgically implanted ultrasonic transit-time flow probe. For volume flow rates ranging from 60 to 750 mL/min, agreement was very good, with a Pearson correlation coefficient of 0.97 (p < 0.0001) and a mean bias of −4.2%. The combination of 2-D matrix array technology and fast processing gives this Doppler method clinical potential, as many of the user- and system-dependent parameters of previous methods, including explicit vessel angle and diameter measurements, are eliminated.

Myocardial perfusion cardiovascular magnetic resonance: optimized dual sequence and reconstruction for quantification

BackgroundQuantification of myocardial blood flow requires knowledge of the amount of contrast agent in the myocardial tissue and the arterial input function (AIF) driving the delivery of this contrast agent. Accurate quantification is challenged by the lack of linearity between the measured signal and contrast agent concentration. This work characterizes sources of non-linearity and presents a systematic approach to accurate measurements of contrast agent concentration in both blood and myocardium.MethodsA dual sequence approach with separate pulse sequences for AIF and myocardial tissue allowed separate optimization of parameters for blood and myocardium. A systems approach to the overall design was taken to achieve linearity between signal and contrast agent concentration. Conversion of signal intensity values to contrast agent concentration was achieved through a combination of surface coil sensitivity correction, Bloch simulation based look-up table correction, and in the case of the AIF measurement, correction of T2* losses. Validation of signal correction was performed in phantoms, and values for peak AIF concentration and myocardial flow are provided for 29 normal subjects for rest and adenosine stress.ResultsFor phantoms, the measured fits were within 5% for both AIF and myocardium. In healthy volunteers the peak [Gd] was 3.5 ± 1.2 for stress and 4.4 ± 1.2 mmol/L for rest. The T2* in the left ventricle blood pool at peak AIF was approximately 10 ms. The peak-to-valley ratio was 5.6 for the raw signal intensities without correction, and was 8.3 for the look-up-table (LUT) corrected AIF which represents approximately 48% correction. Without T2* correction the myocardial blood flow estimates are overestimated by approximately 10%. The signal-to-noise ratio of the myocardial signal at peak enhancement (1.5 T) was 17.7 ± 6.6 at stress and the peak [Gd] was 0.49 ± 0.15 mmol/L. The estimated perfusion flow was 3.9 ± 0.38 and 1.03 ± 0.19 ml/min/g using the BTEX model and 3.4 ± 0.39 and 0.95 ± 0.16 using a Fermi model, for stress and rest, respectively.ConclusionsA dual sequence for myocardial perfusion cardiovascular magnetic resonance and AIF measurement has been optimized for quantification of myocardial blood flow. A validation in phantoms was performed to confirm that the signal conversion to gadolinium concentration was linear. The proposed sequence was integrated with a fully automatic in-line solution for pixel-wise mapping of myocardial blood flow and evaluated in adenosine stress and rest studies on N = 29 normal healthy subjects. Reliable perfusion mapping was demonstrated and produced estimates with low variability.

Implication of cerebral circulation time in intracranial stenosis measured by digital subtraction angiography on cerebral blood flow estimation measured by arterial spin labeling.

Arterial spin labeling (ASL) magnetic resonance imaging to assess cerebral blood flow (CBF) is of increasing interest in basic research and in diagnostic applications, since ASL provides similar information to positron emission tomography about perfusion in vascular territories. However, in patients with steno-occlusive arterial disease (SOAD), CBF as measured by ASL might be underestimated due to delayed bolus arrival, and thus increased spin relaxation. We aimed to estimate the extent to which bolus arrival time (BAT) was delayed in patients with SOAD and whether this resulted in underestimation of CBF. BAT was measured using digital subtraction angiography (DSA) in ten patients with high-grade stenosis of the middle carotid artery (MCA). Regional CBF was assessed with pseudocontinuous ASL. BATs were nonsignificantly prolonged in the stenotic hemisphere 4.1±2.0 s compared with the healthy hemisphere 3.3±0.9 s; however, there were substantial individual differences on the stenotic side. CBF in the anterior and posterior MCA territories were significantly reduced on the stenotic hemisphere. Severe stenosis was correlated with longer BAT and lower quantified CBF. ASL-based perfusion measurement involves a race between the decay of the spins and the delivery of labeled blood to the region of interest. Special caution is needed when interpreting CBF values quantified in individuals with altered blood flow and delayed circulation times. However, from a clinician's point of view, an accentuation of hypoperfusion (even if caused by underestimation of CBF due to prolonged BATs) might be desirable since it indexes potentially harmful physiologic deficits.

OC21.02: Estimation of oxygen saturation, blood flow and blood perfusion in the fetal brain of normally grown fetuses using ultrasound and MRI techniques

OC21.02: Estimation of oxygen saturation, blood flow and blood perfusion in the fetal brain of normally grown fetuses using ultrasound and <scp>MRI</scp> techniques

Noninvasive Cardiac Output Estimation by Inert Gas Rebreathing in Mechanically Ventilated Pediatric Patients

To assess the feasibility and accuracy of inert gas rebreathing (IGR) pulmonary blood flow (Qp) estimation in mechanically ventilated pediatric patients, potentially providing real-time noninvasive estimates of cardiac output. In mechanically ventilated patients in the pediatric catheterization laboratory, we compared IGR Qp with Qp estimates based upon the Fick equation using measured oxygen consumption (VO2) (FickTrue); for context, we compared FickTrue with a standard clinical short-cut, replacing measured with assumed VO2 in the Fick equation (FickLaFarge, FickLundell, FickSeckeler). IGR Qp and breath-by-breath VO2 were measured using the Innocor device. Sampled pulmonary arterial and venous saturations and hemoglobin concentration were used for Fick calculations. Qp estimates were compared using Bland-Altman agreement and Spearman correlation. The final analysis included 18 patients aged 4-23 years with weight >15 kg. Compared with the reference FickTrue, IGR Qp estimates correlated best and had the least systematic bias and narrowest 95% limits of agreement (results presented as mean bias ±95% limits of agreement): IGR -0.2 ± 1.1 L/min, r = 0.90; FickLaFarge +0.7 ± 2.2 L/min, r = 0.80; FickLundell +1.6 ± 2.9 L/min, r = 0.83; FickSeckeler +0.8 ± 2.5 L/min, r = 0.83. IGR estimation of Qp is feasible in mechanically ventilated patients weighing >15 kg, and agreement with FickTrue Qp estimates is better for IGR than for other Fick Qp estimates commonly used in pediatric catheterization. IGR is an attractive option for bedside monitoring of Qp in mechanically ventilated children.

Vector Flow Imaging Compared with Conventional Doppler Ultrasound and Thermodilution for Estimation of Blood Flow in the Ascending Aorta

Transverse oscillation (TO) is a real-time ultrasound vector flow method implemented on a commercial scanner. The TO setup was examined on a flowrig with constant and pulsatile flow. Subsequently, 25 patients undergoing cardiac bypass surgery were scanned intraoperatively with TO on the ascending aorta and compared to transesophageal echocardiography (TEE) and pulmonary artery catheter thermodilution (PACTD). On the flowrig, TO had a precision of 5.5%, 9.4% and 14.7%, a percentage error of 18.2%, 14.6% and 40.7%, and a mean bias of 0.4 cm/s, 36.8 ml/min and 32.4 ml/min for velocity and flow rate (constant and pulsatile) estimation. The correlation coefficients for all flowrig evaluations were 0.99 indicating systematic bias. After bias correction, the percentage error was reduced to 11.5%, 12.6% and 15.9% for velocity and flow rate (constant and pulsatile) estimation. In the in vivo setup, TO, TEE, and PACTD had a precision of 21.9%, 13.7%, and 12.0%. TO compared with TEE and PACTD had a mean bias of 12.6 cm/s and -0.08 l/min, and a percentage error of 23.4%, and 36.7%, respectively. The percentage error was reduced to 22.9% for the TEE comparison, but increased to 43.8% for the PACTD comparison, after correction for the systematic bias found in the flowrig. TO is a reliable and precise method for velocity and flow rate estimation on a flowrig. However, TO with the present setup, is not interchangeable with PACTD for cardiac volume flow estimation, but is a reliable and precise angle-independent ultrasound alternative for velocity estimation of cardiac flow.

Measurement of cerebral blood flow using phase contrast magnetic resonance imaging and duplex ultrasonography

Phase contrast magnetic resonance imaging (PC-MRI) and color-coded duplex ultrasonography (CDUS) are commonly used for measuring cerebral blood flow in the internal carotid (ICA) and vertebral arteries. However, agreement between the two methods has been controversial. Recent development of high spatial and temporal resolution blood vessel wall edge-detection and wall-tracking methods with CDUS increased the accuracy and reliability of blood vessel diameter, hence cerebral blood flow measurement. The aim of this study was to compare the improved CDUS method with 3 T PC-MRI for cerebral blood flow measurements. We found that cerebral blood flow velocity measured in the ICA was lower using PC-MRI than CDUS (left ICA: PC-MRI, 18.0 ± 4.2 vs. CDUS, 25.6 ± 8.6 cm/s; right ICA: PC-MRI, 18.5 ± 4.8 vs. CDUS, 26.6 ± 6.7 cm/s, both p < 0.01). However, ICA diameters measured using PC-MRI were larger (left ICA: PC-MRI, 4.7 ± 0.50 vs. CDUS, 4.1 ± 0.46 mm; right ICA: PC-MRI, 4.5 ± 0.49 vs. CDUS, 4.0 ± 0.45 mm, both p < 0.01). Cerebral blood flow velocity measured in the left vertebral artery with PC-MRI was also lower than CDUS, but no differences in vertebral artery diameter were observed between the methods. Dynamic changes and/or intrinsic physiological fluctuations may have caused these differences in vessel diameter and velocity measurements between the methods. However, estimation of volumetric cerebral blood flow was similar and correlated between the methods despite the presence of large individual differences. These findings support the use of CDUS for cerebral blood flow measurements in the ICA and vertebral artery.

Recent Advances in Nuclear Cardiology.

Nuclear cardiology is one of the major fields of nuclear medicine practice. Myocardial perfusion studies using single-photon emission computed tomography (SPECT) have played a crucial role in the management of coronary artery diseases. Positron emission tomography (PET) has also been considered an important tool for the assessment of myocardial viability and perfusion. However, the recent development of computed tomography (CT)/magnetic resonance imaging (MRI) technologies and growing concerns about the radiation exposure of patients remain serious challenges for nuclear cardiology. In response to these challenges, remarkable achievements and improvements are currently in progress in the field of myocardial perfusion imaging regarding the applicable software and hardware. Additionally, myocardial perfusion positron emission tomography (PET) is receiving increasing attention owing to its unique capability of absolute myocardial blood flow estimation. An F-18-labeled perfusion agent for PET is under clinical trial with promising interim results. The applications of F-18 fluorodeoxyglucose (FDG) and F-18 sodium fluoride (NaF) to cardiovascular diseases have revealed details on the basic pathophysiology of ischemic heart diseases. PET/MRI seems to be particularly promising for nuclear cardiology in the future. Restrictive diseases, such as cardiac sarcoidosis and amyloidosis, are effectively evaluated using a variety of nuclear imaging tools. Considering these advances, the current challenges of nuclear cardiology will become opportunities if more collaborative efforts are devoted to this exciting field of nuclear medicine.

Measurement of extracellular volume and transit time heterogeneity using contrast-enhanced myocardial perfusion MRI in patients after acute myocardial infarction.

To assess the ability of dynamic contrast-enhanced myocardial perfusion MRI to measure extracellular volume (ECV) and to investigate the possibility of estimating capillary transit time heterogeneity (CTH) in patients after myocardial infarction and successful revascularization. Twenty-four perfusion data sets were acquired on a 3 Tesla positron emission tomography (PET)/MRI scanner. Three perfusion models of different complexity were implemented in a hierarchical fashion with an Akaike information criterion being used to determine the number of fit parameters supported by the data. Results were compared sector-wise to ECV from an equilibrium T1 mapping method (modified look-locker inversion recovery (MOLLI)). ECV derived from the perfusion analysis correlated well with equilibrium measurements (R² = 0.76). Estimation of CTH was supported in 16% of sectors (mostly remote). Inclusion of a nonzero CTH parameter usually led to lower estimates of first-pass extraction and slightly higher estimates of blood volume and flow. Estimation of the capillary permeability-surface area product was feasible in 81% of sectors. Transit time heterogeneity has a measurable effect on the kinetic analysis of myocardial perfusion MRI data, and Gd-DTPA extravasation in the myocardium is usually not flow-limited in infarct-related pathology. Measurement of myocardial ECV using perfusion imaging could provide a scan-time efficient alternative to methods based on T1 mapping. Magn Reson Med 77:2320-2330, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

A modified breathing pattern improves the performance of a continuous capnodynamic method for estimation of effective pulmonary blood flow.

In a previous study a new capnodynamic method for estimation of effective pulmonary blood flow (COEPBF) presented a good trending ability but a poor agreement with a reference cardiac output (CO) measurement at high levels of PEEP. In this study we aimed at evaluating the agreement and trending ability of a modified COEPBF algorithm that uses expiratory instead of inspiratory holds during CO and ventilatory manipulations. COEPBF was evaluated in a porcine model at different PEEP levels, tidal volumes and CO manipulations (N=8). An ultrasonic flow probe placed around the pulmonary trunk was used for CO measurement. We tested the COEPBF algorithm using a modified breathing pattern that introduces cyclic end-expiratory time pauses. The subsequent changes in mean alveolar fraction of carbon dioxide were integrated into a capnodynamic equation and effective pulmonary blood flow, i.e. non-shunted CO, was calculated continuously breath by breath. The overall agreement between COEPBF and the reference method during all interventions was good with bias (limits of agreement) 0.05 (-1.1 to 1.2) L/min and percentage error of 36%. The overall trending ability as assessed by the four-quadrant and the polar plot methodology was high with a concordance rate of 93 and 94% respectively. The mean polar angle was 0.4 (95% CI -3.7 to 4.5)°. A ventilatory pattern recurrently introducing end-expiratory pauses maintains a good agreement between COEPBF and the reference CO method while preserving its trending ability during CO and ventilatory alterations.

Dual-Energy Perfusion-CT in Recurrent Pancreatic Cancer – Preliminary Results

To evaluate the diagnostic performance of dual energy (DE) perfusion-CT for the differentiation between postoperative soft-tissue formation and tumor recurrence in patients after potentially curative pancreatic cancer resection. 24 patients with postoperative soft-tissue formation in the conventional regular follow-up CT acquisition after pancreatic cancer resection with curative intent were included prospectively. They were examined with a 64-row dual-source CT using a dynamic sequence of 34 DE acquisitions every 1.5 s (80 ml of iodinated contrast material, 370 mg/ml, flow rate 5 ml/s). Weighted average (linearly blended M0.5) 120kVp-equivalent dual-energy perfusion image data sets were evaluated with a body-perfusion CT tool (see above) for estimating blood flow, permeability, and blood volume. Diagnosis was confirmed by histological study (n = 4) and by regular follow-up. Final diagnosis was local recurrence of pancreatic cancer in 15 patients and unspecific postoperative tissue formation in 9 patients. The blood-flow values for recurrence tissue trended to be lower compared to postoperative tissue formation with 16.6 ml/100 ml/min and 24.7 ml/100 ml/min, respectively for weighted average 120kVp-equivalent image data, which was not significant (n.s.) (p = 0.06, significance level 0.05). Permeability- and blood-volume values were only slightly lower in recurrence tissue (n.s.). DE perfusion-CT is feasible in patients after pancreatic cancer resection and a promising functional imaging technique. As only a trend for lower perfusion values in local recurrence compared to unspecific postoperative alterations was found, the perfusion differences are not yet sufficient to differentiate between malignancy and unspecific postoperative alterations for this new technique. Further studies and technical improvements are needed to generate reliable data for this clinically highly relevant differentiation. • DE Perfusion CT is feasible in patients after pancreatic cancer resection.• While reliable differentiation of unspecific postoperative tissue formation from recurrent malignancy cannot be achieved yet, it is within reach.• DE Perfusion CT has the potential to overcome todays limitations of pure morphological diagnosis of recurrent pancreatic cancer. Citation Format: • Fritz F, Skornitzke S, Hackert T et al. Dual-Energy Perfusion-CT in Recurrent Pancreatic Cancer - Preliminary RESULTS. Fortschr Röntgenstr 2016; 188: 559 - 565.

Comparison of non-invasive MRI measurements of cerebral blood flow in a large multisite cohort

Arterial spin labeling and phase contrast magnetic resonance imaging provide independent non-invasive methods for measuring cerebral blood flow. We compared global cerebral blood flow measurements obtained using pseudo-continuous arterial spin labeling and phase contrast in 436 middle-aged subjects acquired at two sites in the NHLBI CARDIA multisite study. Cerebral blood flow measured by phase contrast (CBFPC: 55.76 ± 12.05 ml/100 g/min) was systematically higher (p < 0.001) and more variable than cerebral blood flow measured by pseudo-continuous arterial spin labeling (CBFPCASL: 47.70 ± 9.75). The correlation between global cerebral blood flow values obtained from the two modalities was 0.59 (p < 0.001), explaining less than half of the observed variance in cerebral blood flow estimates. Well-established correlations of global cerebral blood flow with age and sex were similarly observed in both CBFPCASL and CBFPC. CBFPC also demonstrated statistically significant site differences, whereas no such differences were observed in CBFPCASL. No consistent velocity-dependent effects on pseudo-continuous arterial spin labeling were observed, suggesting that pseudo-continuous labeling efficiency does not vary substantially across typical adult carotid and vertebral velocities, as has previously been suggested. Conclusions: Although CBFPCASL and CBFPC values show substantial similarity across the entire cohort, these data do not support calibration of CBFPCASL using CBFPC in individual subjects. The wide-ranging cerebral blood flow values obtained by both methods suggest that cerebral blood flow values are highly variable in the general population.

Evaluation of static and dynamic perfusion cardiac computed tomography for quantitation and classification tasks.

Cardiac computed tomography (CT) acquisitions for perfusion assessment can be performed in a dynamic or static mode. Either method may be used for a variety of clinical tasks, including (1)stratifying patients into categories of ischemia and (2)using a quantitative myocardial blood flow (MBF) estimate to evaluate disease severity. In this simulation study, we compare method performance on these classification and quantification tasks for matched radiation dose levels and for different flow states, patient sizes, and injected contrast levels. Under conditions simulated, the dynamic method has low bias in MBF estimates (0 to [Formula: see text]) compared to linearly interpreted static assessment (0.45 to [Formula: see text]), making it more suitable for quantitative estimation. At matched radiation dose levels, receiver operating characteristic analysis demonstrated that the static method, with its high bias but generally lower variance, had superior performance ([Formula: see text]) in stratifying patients, especially for larger patients and lower contrast doses [area under the curve [Formula: see text] to 96 versus 0.86]. We also demonstrate that static assessment with a correctly tuned exponential relationship between the apparent CT number and MBF has superior quantification performance to static assessment with a linear relationship and to dynamic assessment. However, tuning the exponential relationship to the patient and scan characteristics will likely prove challenging. This study demonstrates that the selection and optimization of static or dynamic acquisition modes should depend on the specific clinical task.

Estimating Blood Flow in Skeletal Muscle Arteriolar Trees Reconstructed from In Vivo Data

BackgroundOur group uses both computational modeling and intravital videomicroscopy to study the regulation of blood flow in the microcirculation of skeletal muscle. Although we are able to obtain nearly complete arteriolar network structure from in vivo experiments, obtaining complete hemodynamic information is much more difficult and time‐consuming. It is also difficult to obtain the full boundary data needed to directly calculate microvascular blood flow and hematocrit distributions. Therefore, the objective of the present work was to develop a computational model that could accurately predict blood flow in skeletal muscle arteriolar trees in the absence of complete boundary data.MethodsWe used arteriolar trees in the rat gluteus maximus muscle (GM) that were reconstructed from montages obtained via intravital videomicroscopy, and incorporated a recently published method for approximating unknown boundary conditions into our existing steady‐state model of two‐phase blood flow. For varying numbers of unknown boundary conditions, we used the new flow model and GM arteriolar geometry to approximately match red blood cell (RBC) flows corresponding to experimental measurements.ResultsWe showed that this method gives errors that decrease as the number of unknown boundary conditions decreases. We also showed that specifying total blood flow into the arteriolar tree decreases the mean RBC flow error and its variance. By varying target values of pressure and wall shear stress required by the model, we showed that results are less sensitive to the target pressure, and we developed a method for estimating the optimal target shear stress.ConclusionWe have developed and validated a computational method that can accurately estimate RBC flow distribution in arteriolar trees in the absence of complete boundary data.Support or Funding InformationFunding: Natural Sciences and Engineering Research Council (NSERC) grant #R4081A03 awarded to DG, NSERC grant #R4218A03 awarded to DNJ, and NSERC CGS‐D Scholarship awarded to BKA.

Application of Organ Clearance to Estimation of the In Vivo Hepatic Extraction Ratio.

Organ clearance, which has been derived from the organ blood flow and extraction ratio (E), has been extensively used by clinical pharmacologists to explain the pharmacokinetics of many drugs in health and disease. For example, the extent of hepatic clearance or E (Eh) of drugs would determine their response to changes in the liver blood flow and/or activities of the metabolizing enzymes. Although Eh may be obtained directly by cannulating internal blood vessels, the method is invasive. Therefore, indirect methods have been used to estimate Eh from the peripheral blood concentration-time data after intravascular administration of drugs. Additionally, these indirect methods require an estimate of the liver blood flow in the patients or animals. However, some investigators use plasma concentrations and/or liver plasma flow for the estimation of Eh, which could potentially result in significant errors. It is shown here that when plasma concentrations are used along with liver blood flow, an overestimation or underestimation of the true value will result if the blood: plasma concentration (B:P) ratio is >1 or < 1, respectively, with the estimated Eh being different from the true value by a factor equal to the B:P ratio. On the other hand, the use of plasma concentrations and plasma liver flow will always result in an overestimation of the true Eh unless the drug does not penetrate the red blood cells. It is concluded that for the accurate estimation of Eh from the in vivo data, the blood concentration and blood flow should be used.

Probability density function of the electric field in diffuse correlation spectroscopy of human bone in vivo.

Diffuse correlation spectroscopy (DCS) is the technique of choice for non-invasive assessments of human bone blood flow. However, DCS classical algorithms are based on the fundamental assumption that the electric field of the light reaching the DCS photodetector is a zero-mean complex Gaussian variable. The non-validity of this hypothesis might produce inaccurate blood flow estimations. It is shown that for the human tibia, the "Gaussian hypothesis" holds for interoptode distances ≥20 mm. This lower boundary seems to depend on the type of investigated tissue.