Microcirculatory Level Research Articles

A Microfluidic-Based Arteriolar Network Model for Biophysical and Bioanalytical Investigations

The microcirculation plays a key role in the delivery of essential substrates for oxidative processes in cells, the removal of products of cell metabolism, and the regulation of peripheral blood flow distribution. The functional properties of microvascular networks strongly depend on the rheological properties of blood and on the heterogeneity of their architecture. However, studying blood flow behaviour through in vivo microvascular systems is limited by ethical, economical and technical issues. Such limitations have opened the way to in vitro models, such as straight microcapillaries or network- like microchannel constructs, but current in vitro models present simplifications in the architecture design which result in the impossibility of faithfully reproducing key features of the in vivo microvascular haemodynamics. In the present study we report the development of a microfluidic-based in vitro model of the human arteriolar system, characterised by circular channel cross-section, network asymmetry and the presence of both bifurcation- and side-branches. The developed microdevice allows for the quantification of the velocity fields, cell-depletion layer thickness and haematocrit distribution within biomimetic microchannel networks. Results show the potential of our in vitro model in reproducing key features of blood flow behaviour which have been detected for microvascular systems in vivo, including the relationships between cell-depletion layer thickness, haematocrit and vessel diameter. The developed microdevices can find extensive applications in biological and biophysical research, where the mimicking of flow dynamics at the microcirculatory level is required.

Mechanisms underlying blood–brain barrier dysfunction in brain pathology and epileptogenesis: Role of astroglia

Astrocytes are increasingly recognized as equal partners to neurons, also contributing to neurologic disorders such as epilepsy. Activated astrocytes are a common hallmark in patients with mesial temporal lobe epilepsy and Ammon's horn sclerosis. Blood-brain barrier (BBB) opening during status epilepticus has short-term proepileptic effects, as the ionic composition of serum interferes with neuronal excitability. In the long run, astrocytic uptake of albumin induces transforming growth factor β (TGFβ)-mediated signaling cascades, leading to changes in astrocytic properties. Down-regulation of astrocytic inward rectifier K(+) channels and altered surface expression of the water channel, aquaporin 4 results in disturbances in spatial K(+) buffering, thereby rendering the tissue more seizure prone. The expression of astrocytic gap junctional proteins connexin 43 (Cx43) and connexin 30 (Cx30) is altered in epilepsy, and changes in gap junctional communication were found in sclerotic hippocampal tissue in animal models of epilepsy. Although gap junctional communication might exert both proepileptic and antiepileptic effects, double knock out of Cx43 and Cx30 resulted in occurrence of spontaneous epileptiform events. Seizures are associated with massive increases in cerebral blood flow in order to cover the increased energy demand. Hemodynamic responses at the microcirculation level are mediated by astrocyte-pericyte interactions, sharing common mechanisms with spatial K(+) buffering. Although many of the astrocytic mechanisms involving spatial K(+) buffering, nitric oxide, adenosine, and metabotropic glutamate receptor (mGluR)-mediated signalling are altered in epilepsy, little is known how these alterations affect neurovascular coupling. In conclusion, astrocytic activation preceding alterations in neuronal function might critically contribute to epileptogenesis. Therefore, astrocytes represent a promising new target for the development of antiepileptic drugs.

Impaired formation of vasodilators in peripheral tissue in essential hypertension is normalized by exercise training

This study examined vascular function and the adenosine system in skeletal muscle of patients diagnosed with essential hypertension (n = 10) and of normotensive (n = 11) patients, before and after aerobic training. : Before and after 8 weeks of aerobic training, the patients completed experiments in which leg blood flow was determined during infusion of adenosine, acetylcholine and during exercise (20 W); muscle interstitial fluid and femoral venous plasma were sampled via microdialysis probes during baseline conditions, exercise and adenosine infusion and resting muscle biopsies were obtained from muscle vastus lateralis. Before training, leg vascular conductance in response to arterial adenosine infusion was similar in the hypertensive and normotensive groups and the individual vascular response was positively correlated to that of both acetylcholine infusion (r = 0.66, P < 0.001) and exercise (r = 0.72, P < 0.001). Before training, interstitial adenosine concentrations during exercise and prostacyclin (PGI2) concentrations after adenosine infusion were lower in the hypertensive than the normotensive group (P < 0.05). In the hypertensive group, training did not affect the vasodilatory response to arterially infused adenosine but increased the formation of interstitial adenosine and PGI2 and lowered blood pressure. In the normotensive group, training resulted in lower (P < 0.05) leg vascular conductance in response to arterial adenosine infusion. The present data suggest that essential hypertension is associated with a reduced capacity to form adenosine and PGI2 at the skeletal muscle microcirculatory level, which is likely to contribute to the increased peripheral vascular resistance related to the disease. This impairment in vasodilator formation can be normalized by aerobic training.

Efficiency and tolerability of 0,1% tacrolimus ointment in the treatment of patients with moderate atopic dermatitis. Effect of the medication on the skin microcirculation

The article covers modern concepts of the influence of calcineurin inhibitors on formation and liberation inflammatory cytokines and their immunomodulating ability. Goal: to estimate efficiency and bearableness of 0,1 % Tacrolimus ointment (Protopik) at treatment of atopic dermatitis of moderate severity and eczema of hands as supporting therapy, and also influence of a preparation on microcirculation in skin. Materials and methods. In research took part 35 patients having atopic dermatitis (ATD) of moderate severity. The preparation Protopik (0,1% ointment) was used externally by daily thin layer on well cleared skin 2 times a day before clinical improvement, but not less than 2 weeks. Further, at achievement of clinical remission, it was recommended to use a preparation 2 times a week on the sites of skin which are usually struck at aggravations. In other days it was recommended to patients to use a relipidant. To patients with atopic dermatitis before the beginning of treatment and in 1 month from the beginning of application of a preparation by means of Doppler monitoring research microcirculation level in skin (volume speed of a blood-groove) was estimated. Results. High activity of a preparation as means of long supporting therapy is shown. Continuous application of a preparation within 2 weeks allows to reach in most cases almost complete remission. According to Doppler monitoring research, microcirculation in skin at patients with ATD after external application of 0,1% Tacrolimus ointment (Protopik) amplified that it is possible to explain decrease in an infiltration in a dermis. Use of a preparation differs sufficient comfort, and individual complaints to local irritation in the area where the ointment was applied were transient by nature.

The adenosine system in skeletal muscle of individuals with essential hypertension and the effect of physical training

The study examined vascular function and the adenosine (ADO) system in skeletal muscle of individuals diagnosed with essential hypertension (EH; N=10) and normotensive (N; N=11) individuals, before and after a period of aerobic training. Before and after the training period, the subjects participated in two experiments in which a) leg blood flow was determined during arterial infusion of ADO, acetylcholine (ACh) or during exercise, and b) interstitial fluid was sampled from v. lateralis muscle during exercise and ADO infusion. Leg vascular conductance (LVC) in response to arterial ADO infusion was similar in the EH and N group. Interstitial ADO formation during exercise was lower in the EH than the N group. In EH, the period of training did not affect vasodilator responsiveness to arterially infused ADO but improved the formation of interstitial ADO and prostacyclin. In the N group, training resulted in a lower LVC in response to arterial ADO infusion, which was paralleled by a lower leg blood flow during submaximal exercise. In conclusion, whereas the responsiveness to circulating ADO in individuals with essential hypertension remained unaltered with training, the capacity to form ADO and prostacyclin at the microcirculatory level was enhanced, suggesting an improvement in microvascular blood flow regulation. In normotensive individuals, aerobic training reduced the vasodilatory response to intraluminal ADO.

Microvascular Diseases: Is A New Era Coming?

The microvascular bed is an anatomical entity which comprises myriads of small arterioles, capillaries and venules. Microvessels and surrounding tissue metabolism are tightly coupled; consequently they are equipped with many, very specific and fine-tuned mechanisms allowing permanent, precise regulation of nutrient delivery. The review thoroughly describes the structure and physiology of arterioles and capillaries as well as the specialized means to investigate them. Microcirculation has been largely neglected for decades, mainly because of lack of technical possibilities for visualization and quantitation. However the past years have completely renewed the scientific interest, due to the combination of the availability of new techniques in human research and the recognition that the microcirculation is autonomically and causally involved in diseases previously thought to be essentially a question of macrocirculation. Today we start to see that microangiopathy is not only a consequence of large vessel diseases but can be the source of many pathologies in both cardiovascular and metabolic disorders, the best example -developed here- being the cardiometabolic syndrome or prediabetes. With very few exceptions, pentoxifylline and the antidiabetic metformin, no specific treatments have been developed for treating disorders at the microcirculatory level. Metformin has unique, intrinsic actions specifically at the level of terminal arterioles, which are completely independent of its antidiabetic effect. Other drugs are shortly described which have revealed a potential interest in this field. Our review aims at showing that microcirculation is entering a new era, starting with rapidly increasing knowledge of its intimate functioning and worth specific pharmacological developments.

163 XANTHOHUMOL SUPPRESSES HEPATIC INFLAMMATORY RESPONSE TO ACUTE LIVER INJURY

Conclusion: Combining vascular corrosion casting and micro-CT imaging allows (i) to quantify the hepatic vascular anatomy up to the microcirculation level, and (ii) to model hepatic perfusion. This approach may lead to novel insights into liver microcirculation, that can be used to study normal and pathological liver perfusion in the future. Acknowledgment: This research was supported by the Agency for Innovation by Science and Technology in Flanders (IWT), Belgium.

Comparative Assessment of Endothelium-Associated Correction of Experimental Osteoporosis with Resveratrol and Etoksidol

Osteoprotective action of resveratrol and etoksidol was studied on the model of experimental osteoporosis (140 female Wistar rats). It was detected that endothelial dysfunction of bone tissue microcirculation bed that led to osteoporosis development. In contrast to etoksidol, resveratrol prevented the reduction of bone tissue microcirculation level and the aggravation of bone remodeling processes in developing osteoporosis that was manifested by delayed bone trabeculae thinning and averting of microfractures in them.

Use of aspiration thrombectomy in a 102-year-old patient with acute inferior ST-segment elevation myocardial infarction

It has been demonstrated that primary percutaneous coronary intervention (PPCI) is the best treatment option for ST-segment elevation myocardial infarction (STEMI) [ [1] Keeley E.C. Boura J.A. Grines C.L. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomized trials. Lancet. 2003; 361: 13-20 Abstract Full Text Full Text PDF PubMed Scopus (3518) Google Scholar ]. PPCI is an effective method of epicardial flow restoration. Normal epicardial flow in the infarct-related artery is not equal to the restoration of myocardial perfusion at the microcirculation level. It seems that the main reason for impaired myocardial reperfusion is embolization by thrombus and plaque debris. Recent trials have demonstrated that thrombectomy can improve angiographic results of PPCI [ 2 De Luca G. Suryapranata H. Stone G.W. et al. Adjunctive mechanical devices to prevent distal embolization in patients undergoing mechanical revascularization for acute myocardial infarction: a meta-analysis of randomized trials. Am Heart J. 2007; 153: 343-353 Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar , 3 Dudek D. Mielecki W. Burzotta F. et al. Thrombus aspiration followed by direct stenting: a novel strategy of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction. Results of the Polish–Italian–Hungarian RAndomized ThrombEctomy Trial (PIHRATE Trial). Am Heart J. 2010; 160: 966-972 Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar ].

Review article: Part two: Goal‐directed resuscitation – Which goals? Perfusion targets

Haemodynamic targets, such as cardiac output, mean arterial blood pressure and central venous oxygen saturations, remain crude predictors of tissue perfusion and oxygen supply at a cellular level. Shocked patients may appear adequately resuscitated based on normalization of global vital signs, yet they are still experiencing occult hypoperfusion. If targeted resuscitation is employed, appropriate use of end-points is critical. In this review, we consider the value of directing resuscitation at the microcirculation or cellular level. Current technologies available include sublingual capnometry, video microscopy of the microcirculation and near-infrared spectroscopy providing a measure of tissue oxygenation, whereas base deficit and lactate potentially provide a surrogate measure of the adequacy of global perfusion. The methodology and evidence for these technologies guiding resuscitation are considered in this narrative review.

The Mechano-Activated Potassium Channel from Human Erythrocyte (HEMKCA): Effect of Oxidative Stress and its Implication on the Senescence Process

Human erythrocyte (hRBC) shows a tightly controlled programmed cell death with a live span of 120 days. But, as these cells lack nucleus and organelles several question arises: Which are the molecular entities behind this biological clock? How is this process controlled? A widely held hypothesis proposes that hRBC membranes at microcirculation level are exposed to mechanical shear, and somehow these periodical changes lead to the senescence process of these cells. Using Patch Clamp we had characterized a mechano-activated K+ channel (HEMKCA), which shows a sigmoid dependence of Po on applied pressure, a mean conductance of 17pS, and is Ca2+ modulated (140mMKCl,10mMNaCl,1mMCaCl2,pH7.0)(1,2), We had proposed a new hypothesis for the process of senescence, with this channel as the molecular entity behind the biological clock. At the microcirculation level, by means of the O2/CO2 interplay, these membranes are exposed to an oxidative stress. Here, we present the effects of the oxidazing agent tert-Butyl hydroperoxide on the HEMKCA activity. The Po of the channel is dramatically reduced by approximately one order of magnitude, this effect being dependent on the concentration of the oxidizing agent (0μM to 25μM). However the burst mode activity, normally at 17.43±17.15 events/burst, gets diminished only by approximately 25%, similarly, the open dwell time presents only a fall of 40% under the same conditions. Although there is an effect on the intraburst variables, the dramatic effect on Po seems more likely to be related to the opening mechanism. Here we present a partial kinetic model for this channel, and the oxidative stress is presented as a downregulation mechanism for the senescence process of the Human Red Blood Cell. (1)(2005) Biophys. J.88(1):593. (2)(2008) Biophys. J.91(1):1101.

Skin Microcirculation in Primary Arterial Hypertension

Laser Doppler Fluxometry (LDF) was used to assess basic flow (PP) of microcirculation (mc) of dorsal hand skin in 10 healthy persons of both sex (k) – of age 41,3 ± 7,18 years and 10 persons suffering from primary arterial hypertension (nt) – of age 41,3 ± 10,95 years. In obtained record it has beed evaluated: basic flow (PP – in arbitray units of perfusion – PU) and, by analysing frequency spectrum – heart rhythm (RS) and its variation (ZRS), respiratory rhythm (RO), myogenic rhythm of precapillary sphincters tone (RM) and its amplitude (RMa), neurogenic rhythm of precapillary sphincters tone (RN) and its amplitude (NRa) and endothelium-dependent rhythm of precapillary sphincters tone (RE) and its amplitude (REa). The rhythm was assessed in cycles per minute (Hz) and the amplitude by value of signal power in arbitrary units. Means (x¯ ) and standard deviations (± SD) were defined; differences were assessed using t-Student test. In the group of individuals, suffering from arterial hypertension, the decrease of heart rhythm variability, acceleration of respiratory rhythm and neurogenic rhythm on the microcirculation level was observed, what testifies to higher sympathetic activity. In people with arterial hypertension such regularity was not observed, which can prove the endothelium dysfunction. LDF enables complex, noninvasive assessment of circulatory system functioning that can be widely used in clinical

Endothelial dysfunction, inflammation, and oxidative stress in obese children and adolescents: markers and effect of lifestyle intervention

With an increasing prevalence, pediatric obesity is often a prelude to adulthood obesity, and represents a major public health issue. Comorbidities are very common and severe in obese adults, justifying the search for earlier markers or risk factors for cardiovascular diseases in obese children. Endothelial dysfunction has been found to be present in the early stages of atherosclerosis, and can be non-invasively assessed with widely accepted and well-standardized techniques at the macrocirculation level. Endothelial dysfunction at the microcirculation level is less documented in obese children. Obesity in children has been repeatedly and independently correlated to endothelial dysfunction, inflammation and oxidative stress markers, although the relationship between these factors remains to be investigated. However, this would not only allow substantial improvements in risk stratification, but also provide essential data regarding the evolution of endothelial dysfunction in childhood obesity, especially during puberty when pro-inflammatory and pro-oxidative changes, with relative insulin resistance, occur. Therapeutic strategies such as lifestyle interventions in early childhood obesity appear all the more necessary, optimally including both exercise and diet because of their known effects on inflammatory and oxidative stress markers, potentially reversing endothelial dysfunction.

Abstract 9481: Whole Body Periodic Acceleration, Novel Passive Exercise Devices, Enhances Blood Supply to Ischemic Hindlimb in Mice and Human

Introduction: Whole body periodic acceleration (WBPA) is a non-invasive, passive exercise device that has been shown to improve endothelial function by increasing shear stress by head-to-foot direction movements of the body. However, the impact of WBPA on blood flow to ischemic legs has not been investigated. Hypothesis: WBPA enhances blood supply in a mouse model of hindlimb ischemia and in patients with peripheral arterial disease (PAD). Methods and Results: After unilateral femoral artery excision, wild type mice were assigned to either the WBPA (n=15) or control (n=13) group. WBPA was applied at 150 cpm for 45 min under anesthesia once a day. WBPA significantly increased blood flow recovery at 7 and 14 days after surgery as determined by laser doppler perfusion imaging. Sections of ischemic adductor muscle stained with anti-CD31 antibody showed a significant increase in capillary density in WBPA-treated mice compared with control mice, suggesting that WBPA promotes angiogenesis at a microcirculatory level. WBPA increased the phosphorylation of endothelial nitric oxide synthase (eNOS) in adductor muscle. The pro-angiogenic effect of WBPA on ischemic limb was blunted in eNOS-deficient mice, suggesting that the stimulatory effects of WBPA on revascularization are eNOS-dependent. Quantitative real-time PCR analysis showed significant increases in molecules involved in angiogenesis, such as VEGF, FGF2, SDF-1, PDGF-B in ischemic hindlimb by WBPA. Protein array analysis showed that WBPA induced changes in the expression profile of serum angiogenesis-related proteins. Facilitated blood flow recovery was observed in a mouse model of diabetes despite no changes in glycemic control. Clinically, 10 patients (age, 69±7 years, 9 men) with PAD underwent single session of WBPA treatment at 140 cpm for 45 min. WBPA significantly improved the ischemic/non-ischemic ratio of blood flow in the lower extremity from 0.74±0.21 to 0.87±0.21 (p&lt;0.05). Conclusions: WBPA increased blood supply to ischemic lower extremities through activation of eNOS signaling and upregulation of pro-angiogenic growth factor in ischemic skeletal muscle. WBPA is a potentially suitable non-invasive intervention to facilitate therapeutic angiogenesis.

Clinical Features of Early Myocardial Rupture of Acute Myocardial Infarction

We assessed the clinical features of patients with myocardial rupture within 48 to 72 hours, defined as early myocardial rupture, after percutaneous coronary intervention (PCI) for ST-segment elevation acute myocardial infarction (STEMI). Six patients (4 men, 66 ± 13 years) with early myocardial rupture were identified from 1252 consecutive patients undergoing PCI for STEMI. We evaluated the degree of microvascular reperfusion using thrombolysis in myocardial infarction (TIMI) myocardial perfusion (TMP) grade and a resolution of sum of ST-segment elevation in a 12-lead electrocardiogram (ECG). Time from PCI to myocardial rupture was 11 ± 7 hours. All patients showed TMP grade 0 or 1 and an increase in sum of ST-segment elevation after PCI (1.9 ± 0.5 vs 2.5 ± 0.7 mV; P = .032), suggesting severely failed reperfusion at the level of microcirculation as the common feature to develop early myocardial rupture after PCI for STEMI.

Red blood cell transfusions and tissue oxygenation in anemic hematology outpatients

There is little clinical evidence that red blood cell (RBC) transfusions improve oxygen availability at the microcirculatory level. We tested the hypotheses that anemia in chronically anemic patients with relatively healthy microcirculation would be associated with low tissue hemoglobin (Hb) and tissue oxygenation levels and that these conditions would be improved after RBC transfusions. Near-infrared spectroscopy (NIRS) was used to determine tissue oxygen saturation (StO(2)) and tissue Hb index (THI; an index of the amount of Hb in the NIRS measurement volume) in the thenar eminence and sublingual tissue before and 30 minutes after RBC transfusions in 20 chronically anemic hematology outpatients. Data are presented as median (25%-75%). The patients received three (two to three) bags of RBCs in saline-adenine-glucose-mannitol with an age of 21 (7-21) days, which was infused intravenously at the rate of 0.7 bag/hr. RBC transfusions significantly increased hematocrit level from 26% (24%-28%) to 32% (30%-34%; p < 0.0001), Hb level from 8.2 (7.6-8.9) g/dL to 11.0 (9.9-11.8) g/dL (p < 0.0001), whole blood viscosity from 3.4 (3.1-3.5) mPa/sec to 4.2 (4.0-4.5) mPa/sec (p < 0.0001), thenar StO(2) from 81% (80%-84%) to 86% (81%-89%; p = 0.002), thenar THI from 11.2 (9.3-13.3) AU to 13.7 (9.7-15.3) AU (p = 0.024), sublingual StO(2) from 86% (81%-89%) to 91% (86%-92%; p < 0.0001), and sublingual THI from 15.2 (13.0-17.4) AU to 17.2 (13.5-19.7) AU (p = 0.040). Although anemia in chronically anemic hematology outpatients was not associated with low StO(2) and THI levels, RBC transfusions were successful in improving these variables.

Dynamic Changes in Microcirculatory Blood Flow during Dobutamine Stress Assessed by Quantitative Myocardial Contrast Echocardiography

Although dobutamine-atropine stress echocardiography (DASE) has been widely used for evaluating patients with coronary artery disease (CAD), dynamic changes that occur at microcirculatory level during each stage of stress have not been demonstrated in humans. We sought to determine variations in myocardial blood flow (MBF) during DASE using quantitative real time myocardial contrast echocardiography (RTMCE). We studied 45 patients who underwent coronary angiography and RTMCE. Replenishment velocity of microbubbles in the myocardium (β) and MBF reserves were obtained at baseline, intermediate stage (70% of maximal predicted heart rate), peak stress, and recovery phase. β and MBF reserves were lower in patients with than without CAD at intermediate (1.65 vs. 2.10; P=0.001 and 2.44 vs. 3.23; P=0.004) and peak (1.63 vs. 3.00; P<0.001 and 2.14 vs. 3.98; P<0.001, respectively). In patients without CAD, β, and MBF reserves increased from intermediate to peak and decreased at recovery, while in those without CAD reserves did not change significantly. Optimal cutoff values of β reserve at intermediate, peak, and recovery were 1.78, 2.09, and 1.70, with areas under the curves of 0.80 (95%CI=0.67-0.94), 0.89 (95%CI=0.79-0.99), and 0.69 (95%CI=0.53-0.85). Sensitivity, specificity and accuracy for detecting CAD at intermediate stage were 68% (95%CI=48-89), 85% (95%CI=71-98), and 78% (95%CI=66-90), at peak stress were 79% (95%CI=61-97), 96% (95%CI=89-100), and 89% (95%CI=80-98), and at recovery were 74% (95%CI=54-93), 65% (95%CI=47-84), and 69% (95%CI=55-82), respectively. RTMCE allows for quantification of dynamic changes in microcirculatory blood flow at each stage of DASE. The best parameter for detecting CAD in all stages was β reserve.

Effects of Pioglitazone and Rosiglitazone on Vascular Function of Mesenteric Resistance Arteries in Rat Genetic Hypertension

Glitazones exhibit beneficial effects in the vascular system, both on large vessels and at a microcirculatory level. We previously reported the effects of glitazones in the aorta of spontaneously hypertensive rats (SHR). We focus now on the acute and long-term actions of these drugs on mesenteric resistance arteries of the SHR. Incubation with pioglitazone or rosiglitazone (10^–5 mol/l) improved endothelium-dependent relaxations to acetylcholine and the endothelial modulation of phenylephrine contractions. Acetylcholine relaxations that were abolished by N^G-nitro-L-arginine methylester were partly recovered by the glitazones, but no effects of these drugs were observed in the presence of indomethacin or indomethacin + L-NAME. Glitazones did not change the contractions to U46619 or the endothelium-independent relaxation to sodium nitroprusside. Three-week oral pioglitazone or rosiglitazone treatment (3 and 10 mg/kg/day, respectively) confirmed the acute experiments. Thus, in microvessels, glitazones improve endothelial function in such a way that they do not alter endothelial nitric oxide release but reduce the production of vasoconstrictor prostanoids from endothelial cells.

Contrast-Enhanced Ultrasound for the Quantitative Assessment of Perfusion of the Supraspinatus Tendon in Different Positions of Abduction

Degenerative and traumatic lesions of the supraspinatus tendon are common. Perfusion of the tendon plays an important role in this context. Contrast-enhanced ultrasound allows us to perform direct and non-invasive evaluations of perfusion, even at the level of microcirculation. We assessed perfusion of the supraspinatus tendon in the right shoulder of 16 right-handed males aged between 20 and 30 years (mean: 24.1 years) with healthy shoulders. Measurements were performed in four regions of interest on the bursal and articular sides of the tendon at different degrees of abduction (0°, 30° and 60°). Abduction was adjusted using a shoulder abduction orthosis. After contrast agent injection (2.4 ml), we assessed perfusion kinetics. Kinetic characteristics were typical of the tendon, including a slow wash-in and wash-out of the contrast agent. There were reproducible and significant regional differences within the tendon. Hypoperfusion was regularly detected in the region above the insertion of the tendon into the anterior lateral aspect of the humeral head, known as the "critical zone". An increase in shoulder abduction from 0° to 30° and 60° did not lead to further changes. Perfusion differences can be detected for different tendinous regions and can be reproduced interindividually, irrespective of joint position. These results may provide an interesting contribution to the discussion of the genesis of rotator cuff lesions and their management.

Advances in CNS tumour imaging

Brain tumours are the second most common group of paediatric malignancies after leukaemia. Unlike those in adults, most paediatric brain tumours are primitive lesions. The most common location is the posterior cranial fossa, where tumours prevail between ages 1 and 11 years. Conversely, tumours occurring in children younger than 1 year and older than 12 years are located more commonly in the supratentorial compartment. Magnetic resonance imaging (MRI) is an invaluable tool for identifying and characterising brain tumours, presurgical planning and evaluating the effectiveness of surgery, chemotherapy and radiotherapy. Advanced MRI modalities, including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and spectroscopy, provide significant additional information regarding quantities, such as tumour cellularity, haemodynamics and metabolism. DWI provides information regarding diffusion of water molecules from which quantitative values, the apparent diffusion coefficient (ADC), can be calculated. The most important application of DWI in the field of brain tumour imaging is in estimation of cellularity, which correlates grossly with tumour grade. Diffusion tensor imaging (DTI) and fibre tractography are important tools for preoperative mapping of brain tumours, including the identification of the anatomical relationship between tumour and functional areas, such as major fibre tracts. PWI measures cerebral haemodynamics at the microcirculation level. The cerebral blood volume (CBV), defined as the volume of blood per unit of brain tissue and expressed in ml/100 g, is the parameter most commonly evaluated in the field of brain tumour imaging. The average relative CBV of high-grade lesions is significantly higher than that of low-grade neoplasms—a direct function of neovascularity, regardless of the integrity of the blood-brain barrier. There are several techniques for performing PWI. The most widely available is T2*-weighted dynamic susceptibility contrast (DSC) imaging, which requires intravenous administration of a bolus of paramagnetic contrast material and rapid acquisition of images over time during the first pass of contrast material through the capillary bed. DSC-PWI poses a number of technical challenges in the paediatric age group, including the need for constant, high-flow contrast material injection by power injectors, and stable, sufficiently sized intravenous access catheters, which may be problematic in the newborn and infant age groups. Arterial spin labelling (ASL), a perfusion technique that does not use an intravenous tracer, while promising, is less widely available in the clinical arena. Its use is currently limited to a few centres where high fieldstrength (i.e. 3 T and higher) magnets are available. Magnetic resonance spectroscopy (MRS) allows noninvasive detection and measurement of normal and abnormal metabolites and plays an important role in the diagnostic work-up of brain tumours in children. Available 1H-MRS techniques include single-voxel and multi-voxel (chemical shift imaging) methods. Acquisition is possible at short (20– 30 ms), intermediate (135–144 ms), and long (270–280 ms) echo times, yielding different possibilities for metabolite identification and peak analysis. In most instances of brain tumours, a pathological spectrum (non-specific for tumour type) consisting of increased choline (Cho)/creatine (Cr) and Disclaimer Dr. Rossi has no financial interests, investigational or offlabel uses to disclose.