Estimation Of Blood Flow Research Articles

Analysis of time derivative of the temperature response of fingers on the brachial occlusion and its relationship with hemodynamic parameters

Objective. The aim of the study was to analyze the time derivative of temperature response of finger phalanges to brachial occlusion and to establish the relationship between the parameters of temperature dynamics and hemodynamic parameters. Materials and methods. To analyze the response to the occlusion, the methods of dynamic thermography and photoplethysmography (PPG) were used. The parameters of the temperature reaction on occlusion in a group of 60 healthy subjects were analyzed. The Shitzer model was used to establish the relationship between temperature dynamics and peripheral hemodynamics. Results. Parameters describing the temperature response of the fingers on occlusion were introduced. It is shown that the time to reach the maximum of the temperature derivative during post-occlusion corresponds to the maximum of the volumetric blood flow. A coefficient of symmetry is proposed that characterizes the curve of the hemodynamic response of the extremity vessels to a sharp restoration of blood flow after removal of the occlusion. The parameters of temperature dynamics paralleled to the changes in hemodynamic parameters. Conclusions. To compare the results of temperature measurements and results of optical methods of blood flow estimation it is advisable to use not the temperature signal but its first derivative. The use of temperature parameters, expressed in degrees, creates the conditions for the development of a quantitative approach to the description of the hemodynamic response to occlusion. The results of the study contribute to the development of noninvasive methods of diagnosing endothelial dysfunction as a harbinger of atherosclerosis.

Optimization of imaging protocols for myocardial blood flow (MBF) quantification with 18F-flurpiridaz PET

The new PET tracer, 18F-flurpiridaz, with high myocardial extraction allows quantitative myocardial blood flow (MBF) estimation from dynamic PET data and tracer kinetic modeling. The goal of this study is to determine the optimal imaging protocols and parameters using a realistic simulation study. The time activity curves (TACs) of different tissue organs from a 30-s infusion time (IT) of 18F-flurpiridaz in a dynamic PET study were extracted from a previous study. The TACs at different time points were incorporated in a series of realistic 3D XCAT phantoms from which the parameters of a 2-compartment model and the ‘true’ MBF of 18F-flurpiridaz were determined. The compartmental model was used to generate TACs from 7 additional ITs. PET projection data from the XCAT phantoms were generated using Monte Carlo simulation. They were reconstructed using an OS-EM reconstruction algorithm with different update number (N) to obtain dynamic PET images. The blood and myocardial TACs were derived from the dynamic images from which the MBF and %MBF error was estimated. The %MBF error decreases with increasing N of the OS-EM and levels off after ∼42. The 30-s IT gave the smallest %MBF error that decreases from ∼0.57% to ∼19.40%. The MBF for 2-min, 4-min, 8-min and 16-min IT were statistically significant different from the MBF for 30-s IT (P<0.05). Too fast or too slow infusion time gave higher %MBF error. The optimal imaging protocol in dynamic 18F-flurpiridaz PET for accurate quantitative MBF estimation was 30-s IT and N of ∼42 for the OS-EM.

Can Hyperpolarized 13C-Urea be Used to Assess Glomerular Filtration Rate? A Retrospective Study.

This study investigated a simple method for calculating the single-kidney glomerular filtration rate (GFR) using dynamic hyperpolarized 13C-urea magnetic resonance (MR) renography. A retrospective data analysis was applied to renal hyperpolarized 13C-urea MR data acquired from control rats, prediabetic nephropathy rats, and rats in which 1 kidney was subjected to ischemia-reperfusion. Renal blood flow was determined by the model-free bolus differentiation method, GFR was determined using the Baumann–Rudin model method. Reference single-kidney and total GFRs were measured by plasma creatinine content and compared to 1H dynamic contrast-enhanced estimated GFR and fluorescein isothiocyanate-inulin clearance GFR estimation. In healthy and prediabetic nephropathy rats, single-kidney hyperpolarized 13C-urea GFR was estimated to be 2.5 ± 0.7 mL/min in good agreement with both gold-standard inulin clearance GFR (2.7 ± 1.2 ml/min) and 1H dynamic contrast-enhanced estimated GFR (1.8 ± 0.8 mL/min), as well as plasma creatinine measurements and literature findings. Following ischemia-reperfusion, hyperpolarized 13C-urea revealed a significant reduction in single-kidney GFR of 57% compared with the contralateral kidney. Hyperpolarized 13C MR could be a promising tool for accurate determination of GFR. The model-free renal blood flow and arterial input function-insensitive GFR estimations are simple to implement and warrant further translational adaptation.

Correlation between arterial spin-labeling perfusion and histopathological vascular density of pediatric intracranial tumors.

Traditional MRI methods for estimation of blood flow in brain tumors require high-flow injection of contrast agents through large-bore intravenous access, which limits their pediatric utility. In contrast, arterial spin-labeling (ASL) can be used without contrast media. This study aimed to evaluate the relationship between tumor blood flow (TBF) measured by ASL and histopathological vascular density in pediatric brain tumors. Nineteen consecutive children were evaluated (10 boys, 9 girls; median age: 6 years; 8 high-grade and 11 low-grade tumors). ASL was performed with a pseudocontinuous labeling time of 1650ms and post-labeling delay of 1525ms. The maximal absolute (aTBF) and relative (rTBF) tumor blood flows were measured. To evaluate the relative vascular area (%Vessel), the total stained vascular area was divided by the whole tissue area. Spearman's rank-order correlation, the Mann-Whitney U test, and receiver operating characteristic analysis were used for statistical analysis. The absolute and relative TBF rates were 4.9-92.9mL/100g/min and 0.17-3.59mL/100g/min, respectively. The %Vessel was 0.6-30.2%. The %Vessel showed a significant positive correlation with TBF (aTBF: r = 0.87, P < 0.0001; rTBF: r = 0.89, P < 0.0001). The TBF rate of high-grade tumors was significantly higher than that of low-grade tumors (aTBF: P = 0.0050, rTBF: P = 0.0036). The rTBF had the best diagnostic performance (area under the curve: 0.89). ASL perfusion imaging without contrast material can be used for accurate evaluation of histopathological vascular density and may be helpful for tumor grading in children.

Early-phase 18F-AV-45 PET Imaging can Detect Crossed Cerebellar Diaschisis Following Carotid Artery Stenosis and Cerebral Hypoperfusion.

Carotid artery stenosis (CAS) may induce cerebral hypoperfusion. Early-phase 18F-Florbetapir (AV-45/Amyvid, 18F-AV-45) positron emission tomography (PET) imaging can provide perfusion-like property (pAV-45) for the estimation of cerebral blood flow (CBF). Supra-tentorial lesions may cause decreased blood flow and metabolism in the contralateral cerebellum known as crossed cerebellar diaschisis (CCD). The aim was to study the occurrence of CCD after CAS using pAV-45 PET. Eleven healthy controls and 21 patients with unilateral CAS were studied. All subjects underwent 18F-AV-45 PET imaging and arterial spin labeling (ASL) CBF magnetic resonance perfusion imaging. The pAV-45 and ASL CBF values were first correlated. Then, cerebral and cerebellar hypoperfusion volume was analyzed. The cerebral and cerebellar perfusion asymmetry indices (AIs) were calculated from the pAV-45 standard uptake value ratios (SUVRs) of bilateral cerebral and cerebellar cortices, respectively. We found that pAV-45 SUVR was significantly correlated to ASL CBF (p&lt;0.0001, r=0.5731). The AI of cerebellar perfusion was negatively correlated to that of cerebral perfusion (p&lt;0.0001, r=-0.8751). Multiple linear regression showed the cerebral AI (p&lt;0.0001) and hypoperfusion volume (p=0.02) but not the infarction severity and CAS degree significantly correlated to cerebellar AI. If the lower limit of 95% confidence interval of cerebellar AI in healthy controls was set as cut-off for positive CCD, the occurrence of CCD correlated to infarction severity in CAS patients (p=0.03). Our results suggest pAV-45 is reliable to study CBF change. Under unilateral CAS, cerebral AI and hypoperfusion severity may determine the occurrence of CCD.

ИНТРАОПЕРАЦИОННАЯ ОЦЕНКА НЕПОСРЕДСТВЕННЫХ РЕЗУЛЬТАТОВ ПОСЛЕДОВАТЕЛЬНОГО КОРОНАРНОГО ШУНТИРОВАНИЯ

Цель. В настоящее время существуют разногласия относительно целесообразности использования кондуитов при операции коронарного шунтирования (КШ) с наложением последовательного или линейного шунта. Цель исследования: оценить параметры кровотока в шунтах разной конструкции.&#x0D; Материалы и методы. Обследованы 145 пациентов, у которых по поводу ишемической болезни сердца (ИБС) и многососудистого атеросклеротического поражения венечных артерий (ВА) в клинике выполнена операция КШ. Параметры кровотока в линейных и последовательных шунтах оценивали и сравнивали по данным флоуметрии.&#x0D; Результаты. Во всех последовательных шунтах отмечены хорошие параметры объемной скорости кровотока (ОСК) – (70,6 ± 30,2) мл/мин, низкое сопротивление кровотока (пульсовой индекс – PІ 1,8); в линейных шунтах – соответственно ОСК – (37,5 ± 20,5) мл/мин, PI 2,1.&#x0D; Обсуждение. Высокая частота ранней окклюзии шунтов часто обусловлена ошибочным выбором техники операции КШ. Флоуметрия является эффективным инструментом периоперационного контроля качества наложенных анастомозов, помогает избежать ранней окклюзии аутографта.&#x0D; Выводы. Высокие показатели ОСК и низкое сопротивление кровотока по последовательным коронарным шунтам подтверждают целесообразность широкого применения метода при многососудистом КШ.

Enhancement of automated blood flow estimates (ENABLE) from arterial spin‐labeled MRI

To validate a multiparametric automated algorithm-ENhancement of Automated Blood fLow Estimates (ENABLE)-that identifies useful and poor arterial spin-labeled (ASL) difference images in multiple postlabeling delay (PLD) acquisitions and thereby improve clinical ASL. ENABLE is a sort/check algorithm that uses a linear combination of ASL quality features. ENABLE uses simulations to determine quality weighting factors based on an unconstrained nonlinear optimization. We acquired a set of 6-PLD ASL images with 1.5T or 3.0T systems among 98 healthy elderly and adults with mild cognitive impairment or dementia. We contrasted signal-to-noise ratio (SNR) of cerebral blood flow (CBF) images obtained with ENABLE vs. conventional ASL analysis. In a subgroup, we validated our CBF estimates with single-photon emission computed tomography (SPECT) CBF images. ENABLE produced significantly increased SNR compared to a conventional ASL analysis (Wilcoxon signed-rank test, P < 0.0001). We also found the similarity between ASL and SPECT was greater when using ENABLE vs. conventional ASL analysis (n = 51, Wilcoxon signed-rank test, P < 0.0001) and this similarity was strongly related to ASL SNR (t = 24, P < 0.0001). These findings suggest that ENABLE improves CBF image quality from multiple PLD ASL in dementia cohorts at either 1.5T or 3.0T, achieved by multiparametric quality features that guided postprocessing of dementia ASL. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:647-655.

Estimating blood flow in skeletal muscle arteriolar trees reconstructed from in vivo data using the Fry approach.

To develop a computational method to accurately predict blood flow in skeletal muscle arteriolar trees in the absence of complete boundary data. We used arteriolar trees in the rat GM muscle that were reconstructed from montages obtained via IVVM, and incorporated a recently published method for approximating unknown b.c.'s into our existing two-phase, steady-state blood flow model. For varying numbers of unknown b.c.'s, we used the new flow model and GM geometry to approximately match RBC flows corresponding to experimental measurements. We showed this method gives errors that decrease as the number of unknown b.c.'s decreases. We also showed that specifying total blood flow decreases the mean RBC flow error and its variability. By varying required target values of intravascular pressure and wall shear stress, we showed results are less sensitive to target pressure. Finally, we developed and validated a method for determining target values, so that network hemodynamics and resistance can be accurately calculated based only on measured or estimated total blood flow. We have developed and validated a computational method that can accurately estimate RBC flow distribution in skeletal muscle arteriolar trees in the absence of complete boundary data.

APOE ε4 ALLELE EFFECT ON WHITE AND GRAY MATTER PERFUSION IN COGNITIVELY NORMAL AND MCI GROUPS

Cerebral perfusion in both white and gray matter may be an indicator of vascular dysfunction and cognition decline. In this study, simultaneous estimates of cerebral blood flow (CBF) and arterial transit time (ATT) using multiple inversion time arterial spin labeling (ASL) was analyzed in cognitively normal and mild cognitive impairment (MCI) groups. Lower CBF and shorter ATT in APOE ε4 carriers may indicate cerebrovascular functional disorder that impacts cognitive function. 87 subjects (62 cognitively normal (23% ε4+) and 25 MCI (48% ε4+); 23M/64F; age: 63.9±7.7) underwent baseline brain MRI exams as part of several on-going studies within the Wake Forest AD Center, including pseudo-continuous ASL to estimate voxel-wise whole brain CBF and ATT in white and gray matters using a partial volume correction. An example CBF and ATT maps are shown in Figure 1. All ASL images were co-registered to T1 weighted structural images and normalized into a study specific template. Age, Sex, BMI, and HbA1C were adjusted and 2-way ANOVA was performed for each voxel. A minimum cluster size was determined with p<0.05 and α=0.05. APOE ε4 carriers showed reduced CBF in a white matter cluster and four gray matter clusters as shown in Figure 2. The white matter hypo-perfusion cluster locates mainly in left sub-lobar region and extends over temporal and parietal lobes. Four small clusters in gray matter are in left hippocampus, thalamus, right lingual, and right hippocampus and amygdala (Table 1). Although were not statistically significant, ATT values measured in the clusters representing lower blood flow are also shorter in the ε4 carriers (Table 2). In addition, the group without ε4 Allele showed a trend of compensatory increased blood flow in MCI while that with ε4 Allele had impaired blood flow. In this small pilot study sample, lower CBF and shortened ATT were observed among APOE ε4 carriers in both white and gray matter and did not significantly differ by cognitive status. These data suggest evidence of that a perfusion abnormality indicative of flow dynamics of arterial stiffness / arteriolosclerosis are seen among ε4 carriers that may contribute to cerebrovascular disorders. CBF and ATT maps in GM and WM from a representative subject (82 yr. old, F). The partial volume fraction of 0.2 was applied to make the maps. Clusters in white and gray matters representing lower blood flow in the group with APOE ε4 Allele.

Expanding Acquisition and Clutter Filter Dimensions for Improved Perfusion Sensitivity.

A method is explored for increasing the sensitivity of power-Doppler imaging without contrast enhancement. We acquire 1-10 s of echo signals and arrange it into a 3-D spatiotemporal data array. An eigenfilter developed to preserve all three dimensions of the array yields power estimates for blood flow and perfusion that are well separated from tissue clutter. This method is applied at high frequency (24-MHz pulses) to a murine model of an ischemic hindlimb. We demonstrate enhancements to tissue perfusion maps in normal and ischemic tissues. The method can be applied to data from any ultrasonic instrument that provides beamformed RF echo data.

Vector velocity estimation of blood flow - A new application in medical ultrasound.

Vector flow techniques in the field of ultrasound encompass different pulse emission and estimation strategies. Numerous techniques have been introduced over the years, and recently commercial implementations usable in the clinic have been made. A number of clinical papers using different vector velocity approaches have been published. This review will give an overview of the most significant in vivo results achieved with ultrasound vector flow techniques, and will outline some of the possible clinical applications for vector velocity estimation in the future.

Variable temporal sampling and tube current modulation for myocardial blood flow estimation from dose-reduced dynamic computed tomography.

Quantification of myocardial blood flow (MBF) can aid in the diagnosis and treatment of coronary artery disease. However, there are no widely accepted clinical methods for estimating MBF. Dynamic cardiac perfusion computed tomography (CT) holds the promise of providing a quick and easy method to measure MBF quantitatively. However, the need for repeated scans can potentially result in a high patient radiation dose, limiting the clinical acceptance of this approach. In our previous work, we explored techniques to reduce the patient dose by either uniformly reducing the tube current or by uniformly reducing the number of temporal frames in the dynamic CT sequence. These dose reduction techniques result in noisy time-attenuation curves (TACs), which can give rise to significant errors in MBF estimation. We seek to investigate whether nonuniformly varying the tube current and/or sampling intervals can yield more accurate MBF estimates for a given dose. Specifically, we try to minimize the dose and obtain the most accurate MBF estimate by addressing the following questions: when in the TAC should the CT data be collected and at what tube current(s)? We hypothesize that increasing the sampling rate and/or tube current during the time frames when the myocardial CT number is most sensitive to the flow rate, while reducing them elsewhere, can achieve better estimation accuracy for the same dose. We perform simulations of contrast agent kinetics and CT acquisitions to evaluate the relative MBF estimation performance of several clinically viable variable acquisition methods. We find that variable temporal and tube current sequences can be performed that impart an effective dose of 5.5mSv and allow for reductions in MBF estimation root-mean-square error on the order of 20% compared to uniform acquisition sequences with comparable or higher radiation doses.

Improved pressure contour analysis for estimating cardiac stroke volume using pulse wave velocity measurement

BackgroundPressure contour analysis is commonly used to estimate cardiac performance for patients suffering from cardiovascular dysfunction in the intensive care unit. However, the existing techniques for continuous estimation of stroke volume (SV) from pressure measurement can be unreliable during hemodynamic instability, which is inevitable for patients requiring significant treatment. For this reason, pressure contour methods must be improved to capture changes in vascular properties and thus provide accurate conversion from pressure to flow.MethodsThis paper presents a novel pressure contour method utilizing pulse wave velocity (PWV) measurement to capture vascular properties. A three-element Windkessel model combined with the reservoir–wave concept are used to decompose the pressure contour into components related to storage and flow. The model parameters are identified beat-to-beat from the water-hammer equation using measured PWV, wave component of the pressure, and an estimate of subject-specific aortic dimension. SV is then calculated by converting pressure to flow using identified model parameters. The accuracy of this novel method is investigated using data from porcine experiments (N = 4 Pietrain pigs, 20–24.5 kg), where hemodynamic properties were significantly altered using dobutamine, fluid administration, and mechanical ventilation. In the experiment, left ventricular volume was measured using admittance catheter, and aortic pressure waveforms were measured at two locations, the aortic arch and abdominal aorta.ResultsBland–Altman analysis comparing gold-standard SV measured by the admittance catheter and estimated SV from the novel method showed average limits of agreement of ±26% across significant hemodynamic alterations. This result shows the method is capable of estimating clinically acceptable absolute SV values according to Critchely and Critchely.ConclusionThe novel pressure contour method presented can accurately estimate and track SV even when hemodynamic properties are significantly altered. Integrating PWV measurements into pressure contour analysis improves identification of beat-to-beat changes in Windkessel model parameters, and thus, provides accurate estimate of blood flow from measured pressure contour. The method has great potential for overcoming weaknesses associated with current pressure contour methods for estimating SV.

Villous Tree Model with Active Contractions for Estimating Blood Flow Conditions in the Human Placenta.

Background:In the human placenta, maternal and fetal bloods exchange substances through the surface of the villous trees: the fetal blood circulates in the villous trees, around which the maternal blood circulates. The blood flows directly influence fetal growth. Stem villi, the main supports of the villous tree, have contractile cells along the axes, whose contractions are expected to influence the blood circulations in the placenta. The displacement is neither measurable nor predictable while non-invasive measurements such as umbilical Doppler waveforms are helpful to predict the histological changes of the villous trees and vascularization in the placenta.Objective:The displacement caused by the contraction of the villous tree is necessary to predict the blood flows in the placenta. Hence, a computational villous tree model, which actively contracts, was developed in this study.Method:The villous tree model was based on the previous reports: shear moduli of the human placenta; branching patterns in the stem villi. The displacement pattern in the placenta was estimated by the computational model when the shear elastic moduli were changed.Results:The results show that the displacement caused by the contraction was influenced by the shear elastic moduli, but kept useful for the blood flows in the placenta. The characteristics agreed with the robustness of the blood flows in the placenta.Conclusion:The villous tree model, which actively contracts, was developed in this study. The combination of this computational model and non-invasive measurements will be useful to evaluate the condition of the placenta.

Optical Coherence Tomography Angiography to Estimate Retinal Blood Flow in Eyes with Retinitis Pigmentosa

Ophthalmologists sometimes face difficulties in identifying the origin of visual acuity (VA) loss in a retinitis pigmentosa (RP) patient, particularly before cataract surgery: cataract or the retinal disease state. Therefore, it is important to identify the significant factors correlating with VA. Nowadays, retinal blood flow in superficial and deep layers can be estimated non-invasively using optical coherence tomography angiography (OCTA). We estimated blood flow per retinal layer by using OCTA; investigated the correlation between VA and other parameters including blood flow and retinal thickness; and identified the most associated factor with VA in patients with RP. OCTA images in 68 of consecutive 110 Japanese RP patients were analysable (analysable RP group). Thirty-two age- and axial length-matched healthy eyes (control group) were studied. In the analysable RP group, the parafoveal flow density in superficial and deep layers was 47.0 ± 4.9% and 52.4 ± 5.5%, respectively, which was significantly lower than that in controls. Using multivariate analysis, we found that the parafoveal flow density in the deep layer and superficial foveal avascular area were the factors associated with VA. Non-invasive estimation of retinal blood flow per retinal layer using OCTA is useful for predicting VA in RP patients.

Fast Plane Wave 2-D Vector Flow Imaging Using Transverse Oscillation and Directional Beamforming.

Several techniques can estimate the 2-D velocity vector in ultrasound. Directional beamforming (DB) estimates blood flow velocities with a higher precision and accuracy than transverse oscillation (TO), but at the cost of a high beamforming load when estimating the flow angle. In this paper, it is proposed to use TO to estimate an initial flow angle, which is then refined in a DB step. Velocity magnitude is estimated along the flow direction using cross correlation. It is shown that the suggested TO-DB method can improve the performance of velocity estimates compared with TO, and with a beamforming load, which is 4.6 times larger than for TO and seven times smaller than for conventional DB. Steered plane wave transmissions are employed for high frame rate imaging, and parabolic flow with a peak velocity of 0.5 m/s is simulated in straight vessels at beam-to-flow angles from 45° to 90°. The TO-DB method estimates the angle with a bias and standard deviation (SD) less than 2°, and the SD of the velocity magnitude is less than 2%. When using only TO, the SD of the angle ranges from 2° to 17° and for the velocity magnitude up to 7%. Bias of the velocity magnitude is within 2% for TO and slightly larger but within 4% for TO-DB. The same trends are observed in measurements although with a slightly larger bias. Simulations of realistic flow in a carotid bifurcation model provide visualization of complex flow, and the spread of velocity magnitude estimates is 7.1 cm/s for TO-DB, while it is 11.8 cm/s using only TO. However, velocities for TO-DB are underestimated at peak systole as indicated by a regression value of 0.97 for TO and 0.85 for TO-DB. An in vivo scanning of the carotid bifurcation is used for vector velocity estimations using TO and TO-DB. The SD of the velocity profile over a cardiac cycle is 4.2% for TO and 3.2% for TO-DB.

Single-scan rest/stress imaging: validation in a porcine model with 18F-Flurpiridaz.

18F-labeled myocardial flow agents are becoming available for clinical application but the ∼2hour half-life of 18F complicates their clinical application for rest-stress measurements. The goal of this work is to evaluate in a pig model a single-scan method which provides quantitative rest-stress blood flow in less than 15minutes. Single-scan rest-stress measurements were made using 18F-Flurpiridaz. Nine scans were performed in healthy pigs and seven scans were performed in injured pigs. A two-injection, single-scan protocol was used in which an adenosine infusion was started 4minutes after the first injection of 18F-Flurpiridaz and followed either 3 or 6minutes later by a second radiotracer injection. In two pigs, microsphere flow measurements were made at rest and during stress. Dynamic images were reoriented into the short axis view, and regions of interest (ROIs) for the 17 myocardial segments were defined in bull's eye fashion. PET data were fitted with MGH2, a kinetic model with time varying kinetic parameters, in which blood flow changes abruptly with the introduction of adenosine. Rest and stress myocardial blood flow (MBF) were estimated simultaneously. The first 12-14 minutes of rest-stress PET data were fitted in detail by the MGH2 model, yielding MBF measurement with a mean precision of 0.035ml/min/cc. Mean myocardial blood flow across pigs was 0.61 ± 0.11mL/min/cc at rest and 1.06 ± 0.19mL/min/cc at stress in healthy pigs and 0.36 ± 0.20mL/min/cc at rest and 0.62 ± 0.24mL/min/cc at stress in the ischemic area. Good agreement was obtained with microsphere flow measurement (slope = 1.061 ± 0.017, intercept = 0.051 ± 0.017, mean difference 0.096 ± 0.18ml/min/cc). Accurate rest and stress blood flow estimation can be obtained in less than 15min of PET acquisition. The method is practical and easy to implement suggesting the possibility of clinical translation.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging Suggests Normal Perfusion in Normal-Appearing White Matter in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system and has been associated with reduced perfusion in normal-appearing white matter (NAWM). The magnitude of this hypoperfusion is unclear. The present study aims to quantify NAWM perfusion with dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in patients with relapsing-remitting (RR) MS and in a control group. The statistical power of a DCE-MRI acquisition to reveal hypoperfusion in MS was estimated using a Monte Carlo simulation: synthetic tissue curves with a contrast-to-noise ratio of 8 were generated for MS patients and control group using perfusion values reported in previous studies. A compartment-uptake model was fitted to these curves, yielding estimates of cerebral blood flow (CBF), cerebral blood volume (CBV), and permeability-surface area product (PS). This was repeated 1000 times. Mean and standard deviation of the resulting distributions were used to calculate the statistical power of a DCE-MRI study to detect perfusion differences between 16 control subjects and 24 MS subjects.In an institutional review board-approved study, patients with RR-MS (n = 24; mean age, 36 years; 17 women, mean Enhanced Disability Status Scale score, 3.25) and patients without history or symptoms of neurological disorder (n = 16; mean age, 49 years; 9 women) underwent a DCE-MRI examination with a previously established MRI protocol (3D SPGR sequence; 2.1 seconds temporal resolution; 44 slices; spatial resolution, 1.7 × 1.7 × 3 mm). Regions were defined manually in the middle cerebral artery; in the frontal, periventricular, and occipital NAWM; in the pons; and in the thalamus, and CBF, CBV, and PS were quantified using a compartment-uptake model.Parameter differences between MS and control groups were evaluated using a mixed linear model with subjects as random effect and controlling for age and sex. A P value of less than 0.05 was considered to indicate statistical significance. For all but one of previously reported effect sizes, the simulation study estimated a statistical power of 80% to 100% to detect reduced CBF in MS. In the patient study, mean (standard deviation) CBF in NAWM was 11.0 (15.1) and 10.4 (8.2) mL/100 mL per minute in the MS and control groups, respectively. Mean CBV in NAWM was 0.50 (0.45) mL/100 mL in the MS group and 0.48 (0.28) mL/100 mL in the control group. Mean values of PS in NAWM were 0.002 mL (0.027)/100 mL per minute in the control group and -0.001 (0.015) mL/100 mL per minute in the MS patients. Differences between patient groups were not statistically significant for CBF, CBV, mean transit time, and PS (P = 0.44, P = 0.20, P = 0.78, P = 0.66, respectively). In both groups, the influence of age on any parameter was nonsignificant. Cerebral blood flow and CBV in the thalamus and pons were significantly higher than in NAWM regions (P < 1e-4); mean transit time was significantly shorter than in NAWM (P < 1e-4). Permeability-surface area product was not significantly different from zero (P > 0.25) in all evaluated regions. Despite high statistical power, we could not confirm previous reports of NAWM hypoperfusion in MS. This indicates that, at least in our patient cohort, potential hypoperfusion is much less pronounced than reported in previous studies.

Clinical Validation of Pain Management Manipulative Therapy for Knee Osteoarthritis With the Squeeze-Hold Technique: A Case Series

ObjectiveThe purpose of this case series was to describe the short-term and long-term clinical effects of a manual technique for treating osteoarthritis (OA) knee pain. MethodsThis study measured of the immediate effect and long-term effect by using a case series of different groups of subjects. Knee OA and activity restriction in patients were evaluated by using the Kellgren-Lawrence (K/L) Grading Scale and the Japanese Knee Osteoarthritis Measure (JKOM) index. In the intervention, lower limb muscles were squeezed by hand for 20 seconds. Each squeeze was performed for both lower limbs. Passive range-of-motion (ROM) exercise was performed on the knee joint. In one set of cases, immediate effects were measured after a one-time treatment with pretreatment and posttreatment outcome measures. Eleven people with knee OA participated in the study. On a visual analogue scale (VAS) for pain, muscle stiffness, and muscular hemodynamics for estimation of muscle blood flow were recorded before and after the squeeze-hold treatment. In another set of cases, the treatment was given to all patients once a week for 6 months, and long-term effects were measured. Data on 5 subjects with knee OA were collected for 6 months after initial treatment. The VAS for pain and JKOM were recorded every month for 6 months. ResultsFor immediate effects, the VAS was 69 ± 21 mm before treatment and 26 ± 22 mm after treatment. Muscle stiffness was 8.8 ± 3.6 (absolute number) before treatment and 3.5 ± 2.1 after treatment. Tissue (muscle) oxygen saturation was 60.1 ± 5.7% before treatment and 65.3 ± 4.8% after treatment. Total hemoglobin was 24.3 ± 3.3 (absolute number) before treatment and 25 ± 2.3 after treatment. A tendency for reduction in OA knee pain and muscle stiffness was observed, and a tendency for increase was observed in the blood flow in the muscle. For long-term effects in all 5 participants (any K/L grade, any JKOM score), OA knee pain and JKOM score improved gradually through 6 months. ConclusionsThe participants in this case series showed improvement in pain and function. These findings indicate the feasibility of a larger study on the squeeze-hold intervention for OA knee pain.

A novel method to estimate blood flow velocity in the left atrial appendage using enhanced computed tomography: role of Hounsfield unit density ratio at two distinct points within the left atrial appendage

Low blood flow velocity in the left atrial appendage (LAA) indicates a high risk of thromboembolism. Although transesophageal echocardiography (TEE) has been the standard method with which to evaluate the LAA blood flow velocity, a clinically noninvasive method is desired. We hypothesized that the ratio of the Hounsfield unit (HU) density at two distinct points within the LAA represents the blood flow velocity in the LAA. We retrospectively investigated 60 consecutive patients with atrial fibrillation (paroxysmal type, n=29) who underwent enhanced computed tomography (CT) and TEE. The peak emptying flow velocity in the LAA (LAAPV) was evaluated using TEE. HU density was measured at proximal and distal sites of the LAA (LAAp and LAAd) on CT images. The LAAd/LAAp ratio was correlated with the LAAPV (P<0.01, r=0.69). Among several indices, the HU ratio was the most significant parameter associated with the LAAPV (β=0.469, CI 28.602-68.286, P<0.001). Receiver-operating characteristic analysis (area under the curve, 0.91) demonstrated that an HU density ratio cutoff of 0.32 discriminated a low LAAPV (<25cm/s) with sensitivity of 90% and specificity of 84%. Flow velocity of the LAA can be estimated by the HU density ratio at distal and proximal sites within the LAA. Our method might be a feasible substitution for TEE to discriminate patients with a reduced LAAPV.