Blood Flow Studies Research Articles

Impact of Gas Delivery Systems on Imaging Studies of Human Cerebral Blood Flow

Purpose. To compare a semiopen breathing circuit with a non-rebreathing (Hudson mask) for MRI experiments involving gas delivery. Methods and Materials. Cerebral blood flow (CBF) was measured by quantitative phase contrast angiography of the internal carotid and basilar arteries in 18 volunteers (20–31 years). In 8 subjects, gases were delivered via a standard non-rebreathing (Hudson mask). In 10 subjects, gases were delivered using a modified “Mapleson A” semiopen anesthetic gas circuit and mouthpiece. All subjects were given 100% O2, medical air, and carbogen gas (95% O2 and 5% CO2) delivered at 15 L/min in a random order. Results. The Hudson mask group showed significant increases in CBF in response to increased FiCO2 compared to air (+9.8%). A small nonsignificant reduction in CBF (−2.4%) was seen in response to increased inspired concentrations of oxygen (FiO2). The Mapleson A group showed significantly larger changes in CBF in response to both increased inspired concentrations of carbon dioxide (FiCO2) (+32.2%, P < 0.05) and FiO2 (−14.6%, P < 0.01). Conclusions. The use of an anaesthetic gas delivery circuit avoids entrainment of room air and rebreathing effects that may otherwise adversely affect the experimental results.

Post-Carotid Endarterectomy Cerebral Hyperperfusion Syndrome : Is It Preventable by Strict Blood Pressure Control?

ObjectiveCerebral hyperperfusion syndrome (CHS) is a serious complication after carotid endarterectomy (CEA). However, the prevalence of CHS has decreased as techniques have improved. This study evaluates the role of strict blood pressure (BP) control for the prevention of CHS.MethodsAll 18 patients who received CEA from February 2009 through November 2012 were retrospectively reviewed. All patients were routinely managed in an intensive care unit by a same protocol. The cerebral perfusion state was evaluated on the basis of the regional cerebral blood flow (rCBF) study by perfusion computed tomography (pCT) and mean velocity by transcranial doppler (TCD). BP was strictly controlled (<140/90 mm Hg) for 7 days. When either post-CEA hyperperfusion (>100% increase in the rCBF by pCT or in the mean velocity by TCD compared with preoperative values) or CHS was detected, BP was maintained below 120/80 mm Hg.ResultsTCD and pCT data on the patients were analyzed. Ipsilateral rCBF was significantly increased after CEA in the pCT (p=0.049). Post-CEA hyperperfusion was observed in 3 patients (18.7%) in the pCT and 2 patients (12.5%) in the TCD study. No patients developed clinical CHS for one month after CEA. Furthermore, no patients developed additional neurological deficits related to postoperative cerebrovascular complications.ConclusionIntensive care with strict BP control (<140/90 mm Hg) achieved a low prevalence of post-CEA hyperperfusion and prevented CHS. This study suggests that intensive care with strict BP control can prevent the prevalence of post-CEA CHS.

Semi-analytical Study of Blood Flow through a Prosthesis Inserted in an Affected Blood Vessel

In this work, a two dimensional model of the flow is considered, with focus on effects of the nonlinearity coefficient of elasticity, variation of the radius and the Young modulus. The model described characterizes the blood flow consecutively in aneurysms, stenoses and prostheses. We obtain in the three cases that the increase in the coeffcient of nonlinearity decreases the axial fluid velocity, and weakly influence the radial velocity. The velocity of the flow remains parabolic, decrease in the aneurys-mal bag, and increase in the stenosis when the severity of blood vessels diseases varies. We found that aneurysms of small widths present high peaks of wall shear stress, and so predisposes to the formation of thrombus. Finally, we determine the maximum value of elasticity that helps to enhance the performance of prosthesis

Computational study of blood flow in lower extremities under intense physical load

This work is aimed at computational study of the blood flow in lower extremities under intense physical load. We present a modified 1D cardiovascular system model describing skeletal-muscle pumping and autoregulation effects on the blood flow in lower extremities. Skeletal-muscle pump effect is introduced as an external time-periodical pressure function applied to a group of veins. The period of this function is associated with the two-stride period during running. The computational study reveals the explicit optimal stride frequency providing the maximum blood flow through the lower extremities. It is shown that the optimal stride frequency depends on personal parameters. The model is validated by a comparison to the stride frequencies of a number of top-level athletes, therefore, providing a method to assess the level of physical conditioning.

Numerical study of heat transfer and blood flow in two-layered porous liver tissue during microwave ablation process using single and double slot antenna

Microwave ablation (MWA) is a process that uses the heat from microwave energy to kill cancer cells without damaging the surrounding tissue. MWA is emerging as an attractive modality for thermal therapy of large soft tissue targets in short periods of time, making it particularly suitable for ablation of liver cancer. The effectiveness of this technique is related to the temperature achieved during the process, as well as the input microwave power and heating time of treatment. The models of heat and blood flow transport have been used extensively in the study of MWA process and a strong tool for predicting the temperature profile, blood velocity profile and coagulation zone. These models play important role in the optimization of devices and economical way to evaluate new hypothetical designs. Furthermore, they can be used as a guideline for the practical treatment. In this work, the interstitial MWA in two-layered porous liver by single slot microwave coaxial antenna (MCA) and double slot MCA is carried out. A complete mathematical model of MWA of the porous media approach is proposed, which uses transient momentum equations (Brinkman model extended Darcy model) and energy equation coupled with electromagnetic wave propagation equation to describe the specific absorption rate (SAR) profile, temperature profile and blood velocity profile within the porous liver. The coupled nonlinear set of these equations is solved using the axisymmetric finite element method (FEM). The role of transport phenomena in two layers porous media (layers of tumor and normal tissue) for advancing the progress in biomedical applications is investigated numerically. The study aims to understand of the influences of antenna type on the SAR profile, temperature profile and blood velocity profile. In particular, the results calculated from a porous media model are compared with the results calculated from a bioheat model as well as the experimental results from previous work in order to show the validity of the numerical results. The results show that the maximum SAR, temperature and blood velocity appears within the porous liver when using a single slot MCA which is higher than when using a double slot antenna. However, the volumetric SAR, temperature and blood velocity profile within the porous liver when using a double slot MCA provides a wider region in porous liver around the slot MCA and has two hot spot zones which occurs in the vicinity of these double slots.

An Approach to Measure Blood Flow in Single Choroidal Vessel Using Doppler Optical Coherence Tomography

To evaluate the absolute blood flow rate in a single choroidal vessel using Doppler optical coherence tomography (OCT). Three choroidal vessels were selected in the right eye of three normal subjects, and were measured with Doppler OCT at a 1020-nm probe wavelength. The pulsatile change of the blood flow was obtained from synchronized measurement of Doppler OCT and plethysmography. Absolute blood flow rates in choroidal vessels were calculated from Doppler OCT volume data. The cyclic change of the blood flow was quantitatively obtained. Absolute blood flow velocities and blood flow rates at peak systole [mean (SD)] were 46.9 (12.5) mm/s and 5.9 (3.6) μL/min, respectively. The coefficient of variation of three sets of measurements [mean (SD)] was 9.3 (4.9%). Doppler OCT and plethysmography provided an accurate quantitative assessment of the blood flow in choroidal vessels. This measurement technique could prove valuable to the study of choroidal blood flow in normal and pathologic conditions.

778 Hemodynamic Supply of the Affected of Nephroblastoma Kidney

PurposeTo study of the hemodynamic supply for the affected of nephroblastoma kidney and compare it with the contralateral kidney.Patientsand methods: We analyzed the data obtained by Doppler studies of blood...

How well do blood flow imaging and collaterals on angiography predict brain at risk?

As endovascular therapy emerges as a principal approach to restore blood flow in the setting of acute stroke, better methods of patient selection need to be developed. Noninvasive studies of blood flow and angiographic results acquired prior to endovascular therapy may help determine areas of brain at risk of infarction and hemorrhagic transformation, both largely determined by the severity of cerebral ischemia. Pathophysiologic measures of collateral flow and perfusion that characterize ischemic severity prior to revascularization may optimize acute stroke decision-making, currently driven by arbitrary time parameters derived from population studies devoid of imaging.

Response of retinal blood flow to systemic hyperoxia as measured with dual-beam bidirectional Doppler Fourier-domain optical coherence tomography.

PurposeThere is a long-standing interest in the study of retinal blood flow in humans. In the recent years techniques have been established to measure retinal perfusion based on optical coherence tomography (OCT). In the present study we used a technique called dual-beam bidirectional Doppler Fourier-domain optical coherence tomography (FD-OCT) to characterize the effects of 100% oxygen breathing on retinal blood flow. These data were compared to data obtained with a laser Doppler velocimeter (LDV).Methods10 healthy subjects were studied on 2 study days. On one study day the effect of 100% oxygen breathing on retinal blood velocities was studied using dual-beam bidirectional Doppler FD-OCT. On the second study day the effect of 100% oxygen breathing on retinal blood velocities was assessed by laser Doppler velocimetry (LDV). Retinal vessel diameters were measured on both study days using a commercially available Dynamic Vessel Analyzer. Retinal blood flow was calculated based on retinal vessel diameters and red blood cell velocity.ResultsAs expected, breathing of pure oxygen induced a pronounced reduction in retinal vessel diameters, retinal blood velocities and retinal blood flow on both study days (p<0.001). Blood velocity data correlated well between the two methods applied under both baseline as well as under hyperoxic conditions (r = 0.98 and r = 0.75, respectively). Data as obtained with OCT were, however, slightly higher.ConclusionA good correlation was found between red blood cell velocity as measured with dual-beam bidirectional Doppler FD-OCT and red blood cell velocity assessed by the laser Doppler method. Dual-beam bidirectional Doppler FD-OCT is a promising approach for studying retinal blood velocities in vivo.

Cerebrovascular protection of β-asarone in Alzheimer's disease rats: A behavioral, cerebral blood flow, biochemical and genic study

Aim of the studyRecent studies have suggested that β-asarone have neuroprotective and cardiovascular protective effects in animal model. However, the influence of β-asarone on cerebrovascular system has not been explored so far. Therefore, present study was designed to determine whether repeated exposures to β-asarone resulted in positive effects on cerebrovascular function in AD rats. Materials and methodsAlzheimer's disease induced rats was established by injecting both d-galactose (d-gal) and aluminum chloride (AlCl3) into abdominal cavity for 42 days. After injection of AlCl3 and d-gal or saline for 28 days, the rats were treated with volume-matched vehicle or β-asarone (25mg/kg, 50mg/kg or 100mg/kg, i.h.) or Nimodipine (40mg/kg, i.g) once daily for consecutive 14 days, respectively. Behavioral responses of animals were assessed in a Morris water maze. CBF was measured by laser Doppler flowmetry. At the end of this period all rats were sacrificed, lactic acid, pyruvic acid content, Na+K+ATPase activity were determined in brain tissue homogenate to estimate the brain biochemical changes and mRNA expression of ET-1, eNOS and APP was measured with real-time RT-PCR method. ResultsThe spatial navigation task latencies, the times through platform zone and the time for the first through platform zone in the target quadrant in probe task, rCBF of right parietal lobe, the contents of lactic acid, pyruvic acid, and the activity of Na–K-ATP of cortex, and ET-1 and eNOS mRNA expression in hippocampus of AG rats were different from those of BG, P<0.05; The level of APP mRNA expression in model control group rats was higher than that in BG, though there was not a statistically significant difference, P>0.05; Compared with AG, HG rats spatial navigation task latencies were shorter, in probe task the times through platform zone in the target quadrant were bigger, rCBF and blood cell concentration of right parietal lobe were higher, the contents of pyruvic acid was lower, the activity of Na–K-ATP was higher, and ET-1 mRNA expression in hippocampus was lower, P<0.05; The level of eNOS and APP mRNA expression in HG rats was lower than that in AG, though there was not a statistically significant difference, P>0.05; ConclusionThe present results suggested that β-asarone may be useful in memory impairment due to its cerebrovascular protection in AD rats and may develop as a therapeutic drug for treatment of AD patients.

Blood flow simulation and vascular reconstruction

In medical practice, bypass grafts are commonly used as an alternative route around strongly stenosed or occluded arteries. In contrast to arterial bifurcations, surgically created anastomosis can be modified with the objective of enabling optimal graft geometry to yield a flow environment that improves its longevity. This paper presents a three dimensional numerical study of blood flow through bypass systems with different geometries. Coupled with the finite element solver a shape optimization framework considering a genetic algorithm is presented. Numerical results show the benefits of understanding blood flow hemodynamic at anastomosis junctions achieving design improvements. Minimizing recirculation zones and flow stagnation can be useful in surgical planning.

Cerebral Blood Flow and Metabolism Measurement Using Positron Emission Tomography before and during Internal Carotid Artery Test Occlusions: Feasibility of Rapid Quantitative Measurement of CBF and OEF/CMRO2

Balloon test occlusion (BTO) of the internal carotid artery (ICA) combined with cerebral blood flow (CBF) study is a sensitive test for predicting the outcome of permanent ICA occlusion. However, false negative results sometimes occur using single photon emission tomography (SPECT). We have recently developed a rapid positron emission tomography (PET) protocol that measures not only the CBF but also the cerebral oxygen metabolism before and during BTO in succession. We measured acute changes in regional CBF and OEF/CMRO(2) before and during BTO in three cases with large or giant cerebral aneurysms using the rapid PET protocol. Although no patients showed ischemic symptoms during BTO, PET studies exhibited mildly to moderately decreased CBF (9∼34%) compared to the values obtained before BTO in all cases. The average OEF during BTO was significantly increased (21% and 43%) than that of before BTO in two cases. The two cases were considered to be non-tolerant for permanent ICA occlusion and treated without ICA sacrifice. Measurement of the CBF and OEF/CMRO(2) using a rapid PET protocol before and during BTO is feasible and can be used for accurate assessment of tolerance prediction in ICA occlusion.

The neurobiology of glucocerebrosidase-associated parkinsonism: a positron emission tomography study of dopamine synthesis and regional cerebral blood flow

Mutations in GBA, the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are common risk factors for Parkinson disease, as patients with Parkinson disease are over five times more likely to carry GBA mutations than healthy controls. Patients with GBA mutations generally have an earlier onset of Parkinson disease and more cognitive impairment than those without GBA mutations. We investigated whether GBA mutations alter the neurobiology of Parkinson disease, studying brain dopamine synthesis and resting regional cerebral blood flow in 107 subjects (38 women, 69 men). We measured dopamine synthesis with (18)F-fluorodopa positron emission tomography, and resting regional cerebral blood flow with H(2)(15)O positron emission tomography in the wakeful, resting state in four study groups: (i) patients with Parkinson disease and Gaucher disease (n = 7, average age = 56.6 ± 9.2 years); (ii) patients with Parkinson disease without GBA mutations (n = 11, 62.1 ± 7.1 years); (iii) patients with Gaucher disease without parkinsonism, but with a family history of Parkinson disease (n = 14, 52.6 ± 12.4 years); and (iv) healthy GBA-mutation carriers with a family history of Parkinson disease (n = 7, 50.1 ± 18 years). We compared each study group with a matched control group. Data were analysed with region of interest and voxel-based methods. Disease duration and Parkinson disease functional and staging scores were similar in the two groups with parkinsonism, as was striatal dopamine synthesis: both had greatest loss in the caudal striatum (putamen Ki loss: 44 and 42%, respectively), with less reduction in the caudate (20 and 18% loss). However, the group with both Parkinson and Gaucher diseases showed decreased resting regional cerebral blood flow in the lateral parieto-occipital association cortex and precuneus bilaterally. Furthermore, two subjects with Gaucher disease without parkinsonian manifestations showed diminished striatal dopamine. In conclusion, the pattern of dopamine loss in patients with both Parkinson and Gaucher disease was similar to sporadic Parkinson disease, indicating comparable damage in midbrain neurons. However, H(2)(15)O positron emission tomography studies indicated that these subjects have decreased resting activity in a pattern characteristic of diffuse Lewy body disease. These findings provide insight into the pathophysiology of GBA-associated parkinsonism.

Physiologic Effects of Xenon in Xenon-CT Cerebral Blood Flow Studies on Comatose Patients

Despite more than 30years of clinical use, questions remain about the safety of xenon gas in Xenon-CT cerebral blood flow (XeCTCBF) studies. In particular, xenon's effect on brain oxygen (PbtO2) in comatose patients is not well defined. Our objective was to assess the effect of a 4.5-min inhalation of 28% stable xenon on several physiologic variables, including intracranial pressure (ICP), cerebral perfusion pressure (CPP), and PbtO2 in comatose patients (Glasgow Coma Scale [GCS] ≤ 8). Thirty-seven comatose patients who underwent 73 XeCTCBF studies were identified retrospectively from a prospective observational database. Changes in MAP, HR, SaO2, EtCO2, ICP, CPP, and PbtO2 measured at the start of xenon administration and every minute for 5min thereafter were assessed. The maximum change in each variable also was determined for each scan to tabulate clinically relevant changes. Statistically, but not clinically significant changes in MAP, HR, and EtCO2 were seen. Xenon had no effect on ICP, and a small, but clinically insignificant decrease in CPP and PbtO2, was observed. There was a varied response to xenon in most measured variables. Clinically significant changes in each were infrequent, and readily reversed with the cessation of the gas. We conclude that xenon does not appear to have a clinically significant effect on ICP, CPP, and PbtO2 and so appears safe to evaluate cerebral blood flow in comatose patients.

Immediate alterations in intestinal oxygen saturation and blood flow after massive small bowel resection as measured by photoacoustic microscopy

PurposeMassive small bowel resection (SBR) results in villus angiogenesis and a critical adaptation response within the remnant bowel. Previous ex vivo studies of intestinal blood flow after SBR are conflicting. We sought to determine the effect of SBR on intestinal hemodynamics using photoacoustic microscopy, a noninvasive, label-free, high-resolution in vivo hybrid imaging modality. MethodsPhotoacoustic microscopy was used to image the intestine microvascular system and measure blood flow and oxygen saturation (So2) of the terminal mesenteric arteriole and accompanying vein in C57BL6 mice (n = 7) before and immediately after a 50% proximal SBR. A P value of less than .05 was considered significant. ResultsBefore SBR, arterial and venous So2 were similar. Immediately after SBR, the venous So2 decreased with an increase in the oxygen extraction fraction. In addition, the arterial and venous blood flow significantly decreased. ConclusionMassive SBR results in an immediate reduction in intestinal blood flow and increase in tissue oxygen utilization. These physiologic changes are observed throughout the remnant small intestine. The contribution of these early hemodynamic alterations may contribute to the induction of villus angiogenesis and the pathogenesis of normal intestinal adaptation responses.

Development of a fetal risk assessment score for the prediction of neonatal outcome in the growth-restricted fetus

Objective: To develop and analyze a fetal risk assessment score (FRAS) that incorporates fetal arterial and venous blood flow studies (BFS), amniotic fluid volume, the non-stress test (NST) and an estimated fetal weight to improve the ability of antenatal testing to identify fetuses at risk for poor perinatal outcome and compare it to the Biophysical Profile (BPP). Study design: The Perinatal data base of the author’s institution was searched for all patients with singleton gestation with the diagnosis of intrauterine growth restriction, and who had both a biophysical profile (BPP) and fetal BFS (umbilical and middle cerebral artery, ductus venosus) within 4 days of delivery. Fetuses with major congenital abnormalities, chromosomal anomalies, or who delivered less than 25 weeks gestation were excluded. A FRAS score was developed by assigning numerical points for increasing abnormal arterial and venous BFS, and one point each for a non-reactive NST, oligohydramnios or if the fetus was small for gestational age. Recommendations for delivery were based on the clinical situation and the results of the Biophysical Profile (BPP); the FRAS score was not available to the attending physician. The FRAS was then compared to the BPP for the prediction of poor neonatal outcome (significant neonatal complications or prolonged hospital stay) using receiver operating characteristic (ROC) curve analysis and χ2 analysis. Results: Two hundred twenty-nine patients were included in the study. The results of the ROC analysis showed that the designed FRAS (area: 0.802) was slightly better than the BPP (area: 0.659) at predicting poor perinatal outcome in a group of growth-restricted fetuses. Conclusion: The study gives support to the hypothesis that combining biophysical tests with BFS will improve the identification of potential high-risk patients at increased risk for poor neonatal outcome, but prospective, randomized studies are needed to confirm this hypothesis.

Microrheological effects of drag-reducing polymers in vitro and in vivo

Soluble long-chain polymers with a molecular mass >106D have been found to significantly reduce resistance to turbulent flow in pipes, thereby increasing flow rate at constant pressure or decreasing pressure at constant flow rate when added to the flowing fluid at minute concentrations (Toms effect). These molecules, named drag-reducing polymers (DRPs), did not affect resistance to laminar flow in a straight tube. Although, the flow conditions associated with the Toms effect do not occur in the cardiovascular system, a number of studies demonstrated that intravenous administration of nanomolar concentrations of DRPs in experimental animals produced significant hemodynamic effects increasing tissue perfusion and decreasing peripheral vascular resistance without affecting blood viscosity and with no direct effect on the tone of the vessel wall and the intraluminal area. The DRPs were successfully applied in animal models of severe hemorrhagic shock, myocardial ischemia and other pathological conditions demonstrating improvement of impaired hemodynamics and animal conditions/survival. In vitro studies of blood flow in microchannels demonstrated that the DRPs reduced flow and phase separations which occur in the vascular system at normal physiological and pathological conditions. This paper reviews some animal and in vitro studies which employed DRPs as blood additives. Furthermore, the potential mechanisms behind the observed polymer effects on blood circulation are discussed.

Basal fMRI differences between pregabalin responders and non-responder in fibromyalgia

There was a comparison study of regional cerebral blood flow between the responder group and the poor responder group to gabapentin in fibromyalgia (FM). Other brain imaging studies, such as positron emission tomography and fMRI, were needed to clarify the pathophysiology of FM and the characteristics of responders to gabapentin treatment. We studied basal fMRI differences between pregabalin responders and non-responder in patients with FM. (Gabapentin is not approved for the treatment of FM in South Korea.) This research included 21 FM patients and 11 normal persons.

Migraine is not primarily a vascular disorder

There is no question that significant vascular changes may occur during a migraine attack. The question is whether these vascular phenomena are a cause or a consequence of migraine pathophysiology and migraine symptoms. While the simplistic appeal of the ‘vascular hypothesis’ of migraine has had remarkable staying power, studies of the clinical features of migraine, and its physiological and pharmacological mechanisms, have provided strong evidence that effectively refutes a primary role for the vasculature in migraine pathogenesis. It is important to start with the concept of migraine as not merely a headache, but rather a multi-faceted clinical phenomenon that can occur over hours to days. Diverse prodromal symptoms including yawning, mood change, neck pain and polyuria, among others, are common, and electronic diary studies have shown that these symptoms may occur up to several hours before the onset of headache (1). Aura symptoms include both positive and negative visual phenomena, and characteristic sensory or language dysfunction. Nausea, light and sound sensitivity, mechanical allodynia, vertigo and fatigue commonly occur before, during, or after headache. These symptoms indicate elaborate changes in brain chemistry and physiology – there is no reasonable explanation of these symptoms based on a primary vascular mechanism. Regarding migraine headache, the ‘vascular hypothesis’ is centered on the premise that migraine pain is caused by vasodilation. A variety of imaging and pharmacological studies, however, have directly challenged this concept. Pioneering blood flow studies performed by Olesen and colleagues (2) found that a migraine attack may include both hypoand hyperperfusion phases. These studies found that the headache component of the attack begins during the hypoperfusion phase and continues into the hyperperfusion phase, but the hyperperfusion may continue long after the headache has ended. Put simply, there is no correlation between blood flow changes and headache. Recent magnetic resonance angiography (MRA) studies have similarly shown no correlation between changes in vascular caliber and headache in either evoked or spontaneous migraine. Schoonman et al. (3) found that while nitroglycerin did evoke some cerebral and meningeal vasodilation, migraine headache did not occur until after the caliber of vessels had returned to baseline. Nagata et al. (4) reported that spontaneous migraine was not associated with any dilation of the middle meningeal artery as measured by MRA. Rahmann and colleagues (5) showed that vasoactive intestinal peptide is a potent dilator of cerebral vessels, yet does not cause headache. Conversely, sildenafil is known to evoke headache and migraine, but does not cause cerebral vasodilation or alteration in cerebrovascular function (6). Taken together, these studies clearly indicate that vasodilation is neither necessary nor sufficient to cause migraine headache. It has also long been assumed that the pulsating quality of migraine pain is a reflection of vascular pulsation. Recent studies by Ahn (7), however, call this assumption into question, suggesting that in most patients the rate of migraine pain pulsation is in fact slower than the arterial pulse rate. In some patients, the rates of pain pulsation were similar to the arterial pulse, but the two rates were observed to come in and out of phase over time. These studies raise the possibility that pain pulsation could be driven by a mechanism involving neural oscillations rather than by perception of the arterial pulse. Multiple acute and preventive medications such as caffeine, ergotamines, triptans, beta-blockers and

The instrumented fetal sheep as a model of cerebral white matter injury in the premature infant.

Despite advances in neonatal intensive care, survivors of premature birth remain highly susceptible to unique patterns of developmental brain injury that manifest as cerebral palsy and cognitive-learning disabilities. The developing brain is particularly susceptible to cerebral white matter injury related to hypoxia-ischemia. Cerebral white matter development in fetal sheep shares many anatomical and physiological similarities with humans. Thus, the fetal sheep has provided unique experimental access to the complex pathophysiological processes that contribute to injury to the human brain during successive periods in development. Recent refinements have resulted in models that replicate major features of acute and chronic human cerebral injury and have provided access to complex clinically relevant studies of cerebral blood flow and neuroimaging that are not feasible in smaller laboratory animals. Here, we focus on emerging insights and methodologies from studies in fetal sheep that have begun to define cellular and vascular factors that contribute to white matter injury. Recent advances include spatially defined measurements of cerebral blood flow in utero, the definition of cellular maturational factors that define the topography of injury and the application of high-field magnetic resonance imaging to define novel neuroimaging signatures for specific types of chronic white matter injury. Despite the higher costs and technical challenges of instrumented preterm fetal sheep models, they provide powerful access to clinically relevant studies that provide a more integrated analysis of the spectrum of insults that appear to contribute to cerebral injury in human preterm infants.