Blood Transit Time Research Articles

Describing the Highly Three Dimensional Right Ventricle Flow

Visualization of the three-dimensional flow within the Right Ventricle (RV) is a challenging issue due to the fully three-dimensional geometry of the ventricular cavity. To date proper characterization and quantification of the RV flow still remains incomplete, and techniques that can be easily applied to current medical imaging are scarce. A method for simulating the highly complex, multi directional flow within the RV is presented by coupling 4D echocardiography imaging with numerical simulations based on the Immersed Boundaries Method (IBM). A novel formulation for accurately computing the space-time distribution of the blood residence time inside the cavity is introduced. Results showed an initial compact vortex forming past the tricuspid orifice at early diastole that quickly breaks into a weakly turbulent flow pattern and rearranges, during systole, into a peculiar stream-wise vortex spinning out towards the pulmonary orifice. This arrangement is maintained when the Ejection Fraction (EF) is reduced from 58 to 32%. The average blood transit time is found to scale almost inversely proportional to the EF. A careful analysis of the residence time permitted to assess the relative significance of the different flow components (from the direct flow, with a residence time less than one heartbeat, to the residual volume, that stagnates in the ventricle) and their distribution in space.

Simultaneous measurement of cerebral blood flow and transit time with turbo dynamic arterial spin labeling (Turbo-DASL): Application to functional studies

A turbo dynamic arterial spin labeling method (Turbo-DASL) was developed to simultaneously measure cerebral blood flow (CBF) and blood transit time with high temporal resolution. With Turbo-DASL, images were repeatedly acquired with a spiral readout after small-angle excitations during pseudocontinuous arterial spin labeling and control periods. Turbo-DASL experiments at 9.4 T without and with diffusion gradients were performed on rats anesthetized with isoflurane or α-chloralose. We determined blood transit times from carotid arteries to cortical arterial vessels (TT(a) ) from data obtained without diffusion gradients and to capillaries (TT(c) ) from data obtained with diffusion gradients. Cerebral arterial blood volume (CBV(a) ) was also calculated. At the baseline condition, both CBF and CBV(a) in the somatosensory cortical area were 40-50% less in rats with α-chloralose than in rats with isoflurane, while TT(a) and TT(c) were similar for both anesthetics. Absolute CBF and CBV(a) were positively correlated, while CBF and TT(c) were slightly negatively correlated. During forepaw stimulation, CBF increase was 15 ± 3% (n = 7) vs. 60 ± 7% (n = 5), and CBV(a) increase was 19 ± 9% vs. 46 ± 17% under isoflurane vs. α-chloralose anesthesia, respectively; CBF vs. CBV(a) changes were highly correlated. However, TT(a) and TT(c) were not significantly changed during stimulation. Our results support that arterial CBV increase plays a major role in functional CBF changes.

Arterial spin labeling MRI study of age and gender effects on brain perfusion hemodynamics.

Normal aging is associated with diminished brain perfusion measured as cerebral blood flow (CBF), but previously it is difficult to accurately measure various aspects of perfusion hemodynamics including: bolus arrival times and delays through small arterioles, expressed as arterial-arteriole transit time. To study hemodynamics in greater detail, volumetric arterial spin labeling MRI with variable postlabeling delays was used together with a distributed, dual-compartment tracer model. The main goal was to determine how CBF and other perfusion hemodynamics vary with aging. Twenty cognitive normal female and 15 male subjects (age: 23-84 years old) were studied at 4 T. Arterial spin labeling measurements were performed in the posterior cingulate cortex, precuneus, and whole brain gray matter. CBF declined with advancing age (P < 0.001). Separately from variations in bolus arrival times, arterial-arteriole transit time increased with advancing age (P < 0.01). Finally, women had overall higher CBF values (P < 0.01) and shorter arterial-arteriole transit time (P < 0.01) than men, regardless of age. The findings imply that CBF and blood transit times are compromised in aging, and these changes together with differences between genders should be taken into account when studying brain perfusion.

Astaxanthin increases choroidal blood flow velocity

Previous studies have reported that astaxanthin (AXT) has antioxidative and anti-inflammatory effects in addition to its ability to shorten blood transit times. As laser speckle flowgraphy (LSFG) can noninvasively visualize the hemodynamics of the choroidal circulation, we used the technique to evaluate whether continuous ingestion of 12mg of AXT per day could increase quantitative blood flow velocity. In this randomized, double-blind, placebo-controlled study, we examined 20 healthy volunteers who ingested 12mg AXT or placebo capsules over a 4-week period. LSFG was measured in the right eyes of all subjects at pre-ingestion, and at 2 and 4weeks after the treatment of AXT. LSFG values were used to calculate the square blur rate (SBR), which is a quantitative index of relative blood flow velocity. A significant increase of the macular SBR was seen 4weeks after AXT ingestion when compared to the pre-ingestion values (Wilcoxon signed-rank test, P = 0.018). In contrast, no statistical difference in the macular SBR was detected in the placebo group (Friedman test, P = 0.598). No subjective or objective adverse events were found after the 12-mg AXT ingestion. Results suggest that administration of AXT over a 4-week period can elevate the choroidal blood flow velocity without any adverse effects.

Perfusion Computed Tomography Findings of Autoimmune Pancreatitis

The aim of this study was to clarify the pancreatic blood perfusion in patients with autoimmune pancreatitis (AIP) and the changes after steroid treatment. Perfusion computed tomography was performed in 11 patients with AIP and 12 control subjects. Pancreatic volumetric blood flow (F(V)), volume of distribution (V(D)), and blood transit time τ were determined from a single-compartment kinetic model. Nine patients with AIP were reexamined by perfusion computed tomography after corticosteroid administration. The pancreatic F(V) values of the 11 patients with AIP (82.7/min) were significantly lower than those of control subjects (163.5/min, P = 0.0006). On the other hand, the pancreatic V(D) and τ values were not significantly different between AIP and normal. After steroid treatment, the F(V) values of 9 reexamined patients with AIP (76.2/min) were significantly elevated (109.8/min, P = 0.0391). However, the changes of the values after the treatment differed in degree among individuals. The values of 4 patients were dramatically elevated to greater than 100/min, whereas those of 4 other patients did not improve well. The value of the remaining patient whose initial F(V) value was normal (168.09/min) did not change after the treatment. Pancreatic volumetric perfusion was attenuated in AIP patients. The perfusion was improved after the steroid treatment.

Pseudo‐random arterial modulation (PRAM): A novel arterial spin labeling approach to measure flow and blood transit times

To investigate blood flow and transit time measurement, using the pseudo-random arterial modulation (PRAM). PRAM is based on a pseudo-random sequence of inversions and noninversions of the arterial blood at a labeling plane inferior to the imaging plane. To accomplish this, a pseudo-continuous tagging is used to create inversion or noninversion prepulses before a gradient echo sequence and tested on phantoms and human volunteers. We have shown here that the PRAM technique can measure the velocity profile and the transit time accurately and efficiently both in a phantom and in vivo in a human brain. PRAM does not require separate control and label acquisition as is common in arterial spin labeling (ASL) but rather measures the distribution of transit times to a voxel within one integrated scan. The PRAM method is a model-free approach in measuring transit time distributions, and therefore ultimately should provide more accurate perfusion measurements.

Counterpoint: Humans do not demonstrate selective brain cooling during hyperthermia

Selective brain cooling is an attractive idea for protection of the central nervous system against fatigue ([17][1]) and potentially cellular damage. Several factors influence fatigue, but brain temperature appears to be of utmost importance for hyperthermia-induced fatigue during prolonged exercise

Circulatory model of vascular and interstitial distribution kinetics of rocuronium: a population analysis in patients

The time-course of the neuromuscular blocking effect of rocuronium depends on circulatory mixing and the rate of distribution into the interstitial space. In order to quantitatively evaluate these processes, a physiologically meaningful model of distribution kinetics based on circulatory transport and interstitial diffusion, was fitted to rocuronium disposition data in 10 patients using a population approach. Information on cardiac output and circulatory mixing was obtained from the kinetics of indocyanine green (ICG), which was injected simultaneously with rocuronium. As a compromise between physiological reality and parameter identifiability, the organs of the systemic circulation were lumped into a heterogeneous subsystem, described by an axially distributed model of extravascular diffusion. Diffusion into the interstitial space determines the rate of rocuronium distribution in the body (diffusional time constant 89 min). The resulting whole body distribution kinetics depends both on cardiac output and on the apparent permeability surface area product (0.16 l/min). The analysis of the ICG data revealed that heterogeneity of blood transit time through the systemic circulation decreased and that cardiopulmonary volume increased, respectively, with cardiac output. The approach should be useful for studying the effect of disease states on distribution kinetics of drugs.

Drug structure–transport relationships

Malcolm Rowland has greatly facilitated an understanding of drug structure–pharmacokinetic relationships using a physiological perspective. His view points, covering a wide range of activities, have impacted on my own work and on my appreciation and understanding of our science. This overview summarises some of our parallel activities, beginning with Malcolm’s work on the pH control of amphetamine excretion, his work on the disposition of aspirin and on the application of clearance concepts in describing the disposition of lidocaine. Malcolm also spent a considerable amount of time developing principles that define solute structure and transport/pharmacokinetic relationships using in situ organ studies, which he then extended to involve the whole body. Together, we developed a physiological approach to studying hepatic clearance, introducing the convection–dispersion model in which there was a spread in blood transit times through the liver accompanied by permeation into hepatocytes and removal by metabolism or excretion into the bile. With a range of colleagues, we then further developed the model and applied it to various organs in the body. One of Malcolm’s special interests was in being able to apply this knowledge, together with an understanding of physiological differences in scaling up pharmacokinetics from animals to man. The description of his many other activities, such as the development of clearance concepts, application of pharmacokinetics to the clinical situation and using pharmacokinetics to develop new compounds and delivery systems, has been left to others.

Effects of feeding on thermoregulatory behaviours and gut blood flow in white sturgeon (Acipenser transmontanus) using biotelemetry in combination with standard techniques

The effects of thermoregulatory behaviours on gut blood flow in white sturgeon Acipenser transmontanus before and after feeding was studied using a blood flow biotelemetry system in combination with a temperature preference chamber. This is the first study to look at cardiovascular responses to feeding in white sturgeon, and also the first time behavioural tests in fish have been combined with recordings of cardiac output, heart rate, cardiac stroke volume and gut blood flow. The results showed strong correlations between gut blood flow and temperature choice after feeding (R(2)=0.88+/-0.03, 6-8 h postprandially and R(2)=0.89+/-0.04, 8-10 h postprandially) but not prior to feeding (R(2)=0.11+/-0.05). Feeding did not affect the actual temperature preference (18.4+/-0.7 degrees C before feeding, 18.1+/-0.7 degrees C, 6-8 h postprandially and 17.5+/-0.5 degrees C, 8-10 h postprandially). Fish instrumented with a blood flow biotelemetry device, and allowed to move freely in the water, had a significantly lower resting heart rate (37.3+/-0.26 beats min(-1)) compared with the control group that was traditionally instrumented with transit-time blood flow probes and kept in a confined area in accordance with the standard procedure (43.2+/-2.1 beats min(-1)). This study shows, for the first time in fish, the correlation between body temperature and gut blood flow during behavioural thermoregulation.

Noninvasive detection of pulmonary tissue destruction in a mouse model of emphysema using hyperpolarized 129Xe MRS under spontaneous respiration

In the present study, a chemical shift saturation recovery method in hyperpolarized (129)Xe MR spectroscopy measurements was applied to two groups of spontaneously breathing mice, an elastase-induced emphysema model and a control group. Parameters detected were those related to lung structures and functions, such as alveolar septal thickness, h, the ratio of the alveolar septal volume relative to gas space volume, V(s)/V(a), and the transit time of blood through the gas exchange region, τ. To investigate the potential of these parameters as biomarkers, an attempt was made to detect physiologic changes in the lungs of elastase-treated mice. Our results showed that V(s)/V(a) was significantly reduced in elastase-treated mice, reflecting emphysema-like destruction of the alveolar wall. Compared with histologic results, this degree of reduction was shown to reflect the severity of wall destruction. On the other hand, significant changes in other parameters, h and τ, were not shown. This study is the first application of hyperpolarized (129)Xe MR spectroscopy to a mouse model of emphysema and shows that the V(s)/V(a) volume ratio is an effective biomarker for emphysema that could become useful in drug research and development through noninvasive detection of pathologic changes in small rodents.

High-field continuous arterial spin labeling with long labeling duration: reduced confounds from blood transit time and postlabeling delay.

In quantitative perfusion imaging using arterial spin labeling, variable blood transit times and postlabeling delays are two confounding factors that may compromise the accuracy of perfusion quantifications. In this study, theoretical analyses and experimental data at 9.4 T demonstrate that increasing labeling duration not only enhances the contrast of the arterial spin labeling signal but also minimizes the effect of variable postlabeling delays in multislice arterial spin labeling acquisitions. With a labeling duration of 6.4 sec, arterial spin labeling signal acquired in multislice mode (11 slices) is very similar to that acquired in single-slice mode. Previous studies have shown that inserting a delay between the spin labeling pulse and the image acquisition pulse could reduce confounds resulting from variable blood transit times at the expense of arterial spin labeling sensitivity. Our simulations suggest that enhancing the contrast of arterial spin labeling signal offers the opportunity for extending the postlabeling delay to a longer duration, minimizing systematic errors associated with a wide range of blood transit times, which could have significant implications for applying arterial spin labeling techniques to perfusion imaging of pathological conditions in animal models.

Possible key residues that determine left gastric artery blood flow response to PACAP in dogs

To determine the effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on left gastric artery (LGA) flow and to unveil the structural or functional important sites that may be critical for discrimination of different receptor subtypes. Peptides, including PACAP-27, PACAP-38, amino acid substituted PACAP-27 and C-terminus truncated analogues PACAP (27-38), were synthesized by a simultaneous multiple solid-phase peptide synthesizer. Flow probes of an ultrasound transit-time blood flowmeter were placed around the LGA of beagle dogs. When peptides were infused intravenously, the blood flow was measured. [Ala4, Val5]-PACAP-27 caused a concentration-dependent vasodepressor action which was similar to that caused by PACAP-27. The LGA blood flow response to [Ala4, Val5]-PACAP-27 was significantly higher than that to PACAP-27, which was similar to that to vasoactive intestinal polypeptide (VIP) at the same dose. [Ala6]-PACAP-27 did not increase the peak LGA flow. [Gly8]-PACAP-27 showed a similar activity to VIP. [Asn24, Ser25, Ile26]-PACAP-27 did not change the activity of peptides at all doses. NH2 terminus is more important to biological activity of peptides and specific receptor recognition than COOH-terminus.

Transit-Time Blood Flow Measurements in Sequential Saphenous Coronary Artery Bypass Grafts

Little information is available on transit-time flow measurements of sequential saphenous vein grafts. The aim of the study was evaluation of mean blood flow and pulsatility index of sequential saphenous vein grafts in a large population of patients operated on with coronary artery bypass grafting. In 581 patients 1,390 grafts were nested into left internal mammary artery to left anterior descending artery, single vein grafts, or double and triple sequential vein grafts, and analyzed. Within the single vein graft group there were no differences between flow of grafts to different target vessels except for diagonals (diagonal versus obtuse marginal, p < 0.001; versus posterior descending artery, p = 0.035; versus right coronary artery, p = 0.003). Flows measured in single vein grafts were significantly lower than in double (p < 0.001) and triple sequential vein grafts (p < 0.001). Flows were lower in double versus triple sequential vein grafts (p = 0.017) and higher in men versus women (p < 0.001). Mean pulsatility index of vein grafts were lower in the left versus the right coronary system, 2.0 +/- 0.01 and 2.4 +/- 0.06, respectively (p < 0.001). Between sex and groups of vein grafts within each coronary system, mean pulsatility index had similar values. Blood flow increases from single to double and up to triple sequential grafts. Single grafts directed to diagonals have the lowest flow. Graft blood flows are higher in male versus female patients. Single, double, and triple saphenous vein grafts have similar pulsatility indexes. Pulsatility index of grafts to the right coronary system is significantly higher than that of grafts to the left coronary system.

Muscular and pulmonary O2 uptake kinetics during moderate‐ and high‐intensity sub‐maximal knee‐extensor exercise in humans

The purpose of this investigation was to determine the contribution of muscle O(2) consumption (mVO2) to pulmonary O(2) uptake (pVO2) during both low-intensity (LI) and high-intensity (HI) knee-extension exercise, and during subsequent recovery, in humans. Seven healthy male subjects (age 20-25 years) completed a series of LI and HI square-wave exercise tests in which mVO2 (direct Fick technique) and pVO2 (indirect calorimetry) were measured simultaneously. The mean blood transit time from the muscle capillaries to the lung (MTTc-l) was also estimated (based on measured blood transit times from femoral artery to vein and vein to artery). The kinetics of mVO2 and pVO2 were modelled using non-linear regression. The time constant (tau) describing the phase II pVO2 kinetics following the onset of exercise was not significantly different from the mean response time (initial time delay + tau) for mVO2 kinetics for LI (30 +/- 3 vs 30 +/- 3 s) but was slightly higher (P < 0.05) for HI (32 +/- 3 vs 29 +/- 4 s); the responses were closely correlated (r = 0.95 and r = 0.95; P < 0.01) for both intensities. In recovery, agreement between the responses was more limited both for LI (36 +/- 4 vs 18 +/- 4 s, P < 0.05; r = -0.01) and HI (33 +/- 3 vs 27 +/- 3 s, P > 0.05; r = -0.40). MTTc-l was approximately 17 s just before exercise and decreased to 12 and 10 s after 5 s of exercise for LI and HI, respectively. These data indicate that the phase II pVO2 kinetics reflect mVO2 kinetics during exercise but not during recovery where caution in data interpretation is advised. Increased mVO2 probably makes a small contribution to during the first 15-20 s of exercise.

Feasibility of Measurement of Pancreatic Perfusion Parameters with Single-Compartment Kinetic Model Applied to Dynamic Contrast-enhanced CT Images

To examine the feasibility of measuring pancreatic perfusion parameters by using a single-compartment kinetic model applied to contrast material-enhanced computed tomographic (CT) images. This study received institutional review board approval and was HIPAA compliant. Informed consent was waived. Eight subjects (four men, four women; median age, 40 years; range, 35-57 years), all potential renal donors with no pancreatic pathologic abnormalities, underwent abdominal CT imaging, which resulted in 30 10-mm-thick sections obtained at a single level. Imaging was a direct result of bolus timing employed for standard renal donor protocol; no additional imaging beyond what was clinically warranted was performed. Images were obtained every 3 seconds; scanning was initiated at the onset of contrast material administration. Region-of-interest measurements were obtained for the pancreatic body and the aorta to generate time-enhancement curves (TECs). A one-compartment model was applied by using the aortic and pancreatic TECs as the input and output functions, respectively. Pancreatic volumetric blood flow F(V), volume of distribution V(D), and blood transit time tau were determined. Modeled pancreatic TECs were generated and were compared with actual TECs for wellness of fit. Pancreatic F(V) values from the single-compartment model ranged from 0.961 to 6.405 min(-1) (mean, 3.560 min(-1) +/- 1.900 [standard deviation]). Volume of distribution V(D) ranged from 1.491 to 3.080 (mean, 2.383 +/- 0.638), while values of tau ranged from -3.090 to 6.436 seconds (mean, 0.481 second +/- 3.000). Modeled pancreatic TECs closely matched true pancreatic TECs for each subject, with R(2) values ranging from 0.840 to 0.959. A simple one-compartment kinetic model can be applied to contrast-enhanced images of normal pancreas to yield accurate pancreatic TECs, which attest to the perfusion parameters obtained. In addition to yielding volumetric blood flow similar to that of other models of tissue perfusion, two additional pancreatic perfusion parameters can be obtained. http://radiology.rsnajnls.org/cgi/content/full/2492080026/DC1.

Modeling and optimization of look‐locker spin labeling for measuring perfusion and transit time changes in activation studies taking into account arterial blood volume

This work describes a new compartmental model with step-wise temporal analysis for a Look-Locker (LL)-flow-sensitive alternating inversion-recovery (FAIR) sequence, which combines the FAIR arterial spin labeling (ASL) scheme with a LL echo planar imaging (EPI) measurement, using a multireadout EPI sequence for simultaneous perfusion and T*(2) measurements. The new model highlights the importance of accounting for the transit time of blood through the arteriolar compartment, delta, in the quantification of perfusion. The signal expected is calculated in a step-wise manner to avoid discontinuities between different compartments. The optimal LL-FAIR pulse sequence timings for the measurement of perfusion with high signal-to-noise ratio (SNR), and high temporal resolution at 1.5, 3, and 7T are presented. LL-FAIR is shown to provide better SNR per unit time compared to standard FAIR. The sequence has been used experimentally for simultaneous monitoring of perfusion, transit time, and T*(2) changes in response to a visual stimulus in four subjects. It was found that perfusion increased by 83 +/- 4% on brain activation from a resting state value of 94 +/- 13 ml/100 g/min, while T*(2) increased by 3.5 +/- 0.5%.

Effects of Astaxanthin on Human Blood Rheology

Effects of astaxanthin (AX) derived from H. pluvialis on human blood rheology were investigated in 20 adult men with a single-blind method. The experimental group was 57.5 ± 9.8 years of age and the placebo group was 50.8 ± 13.1 years of age. A blood rheology test that measures whole blood transit time was conducted using heparinized blood of the volunteers by a MC-FAN apparatus (microchannel array flow analyzer). After administration of AX 6 mg/day for 10 days, the values of the experimental group were decreased from 52.8 ± 4.9 s to 47.6 ± 4.2 s (p<0.01) and a comparison of the values between the experimental (47.6 ± 4.2 s) and the placebo (54.2 ± 6.7 s) groups showed a significant difference (p<0.05). There were no adverse effects resulting from the administration of AX 6 mg/day for 10 days. Informed consent was obtained from each subject.

Analysis of Blood Flow in a Third Ventricular Ependymoma and an Olfactory Bulb Meningioma by using Perfusion Computed Tomography

Brain perfusion computed tomography (CT) scanning was performed in a mongrel dog and a golden retriever that were diagnosed with third ventricular tumor and olfactory bulb tumor, respectively, by contrast-enhanced CT. The tumors were pathologically diagnosed as ependymoma and meningioma, respectively. Perfusion CT results revealed that the ependymoma in this study had a lower blood flow, higher blood volume, and greater transit time of blood than the adjacent brain tissue. Further, the meningioma in this study had a higher blood flow, higher blood volume, and greater transit time of blood than the adjacent brain tissue. Perfusion CT can potentially be used for the grading of brain tumors and narrowing differential diagnosis, provided the perfusion CT data of animals are accumulated.

Modeling systemic and renal gadolinium chelate transport with MRI

The advent of modern MRI scanners and computer equipment permits the rapid sequential collection of images of gadolinium chelate (Gd) transit through the kidney. The excellent spatial and temporal (0.9 s) resolution permits analyzing the shape of the recovered curves with a sophisticated model that includes both space and time. The purpose of this manuscript is to present such a mathematical model. By building into the model significant physical processes that contribute to the shape of the measured curve, quantitative values can be assigned to important parameters. In this work, quantitative values are determined for blood dispersion through the cardio-pulmonary system, systemic clearance rate of Gd, blood flow into each kidney, blood transit time in each kidney, the extraction rate of Gd across the capillary membrane, interstitial distribution volume, and the GFR for each kidney.