Influence of segmented vessel size due to limited imaging resolution on coronary hyperemic flow prediction from arterial crown volume.

Computational predictions of the functional stenosis severity from coronary imaging data use an allometric scaling law to derive hyperemic blood flow (Q) from coronary arterial volume (V), Q = αV(ß) Reliable estimates of α and ß are essential for meaningful flow estimations. We hypothesize that the relation between Q and V depends on imaging resolution. In five canine hearts, fluorescent microspheres were injected into the left anterior descending coronary artery during maximal hyperemia. The coronary arteries of the excised heart were filled with fluorescent cast material, frozen, and processed with an imaging cryomicrotome to yield a three-dimensional representation of the coronary arterial network. The effect of limited image resolution was simulated by assessing scaling law parameters from the virtual arterial network at 11 truncation levels ranging from 50 to 1,000 µm segment radius. Mapped microsphere locations were used to derive the corresponding relative Q using a reference truncation level of 200 µm. The scaling law factor α did not change with truncation level, despite considerable intersubject variability. In contrast, the scaling law exponent ß decreased from 0.79 to 0.55 with increasing truncation radius and was significantly lower for truncation radii above 500 µm vs. 50 µm (P< 0.05). Hyperemic Q was underestimated for vessel truncation above the reference level. In conclusion, flow-crown volume relations confirmed overall power law behavior; however, this relation depends on the terminal vessel radius that can be visualized. The scaling law exponent ß should therefore be adapted to the resolution of the imaging modality.

Intrauterine transfusion combined with partial exchange transfusion for twin anemia polycythemia sequence: modeling a novel technique.

INTRODUCTION: Twin anemia-polycythemia sequence (TAPS) is a newly described disease in monochorionic twin pregnancies, characterized by large inter-twin hemoglobin differences. Optimal management for TAPS is not clear. One of the possible treatment modalities is intrauterine blood transfusion (IUT) in the donor with or without combination of partial exchange transfusion (PET) in the recipient. METHODS: We applied a computational model simulation to illustrate the mechanism of IUT with and without PET in TAPS occurring after laser surgery for twin-twin transfusion syndrome (TTTS). Model simulations were performed with the representative anastomotic pattern as observed during laser intervention, and after placental dye injection. RESULTS: The model was tested against different cases where IUT was combined with PET for the treatment of post-laser TAPS. Model simulations using the observed anastomotic pattern showed a significant reduction of hyperviscosity in the recipient after IUT/PET compared to IUT without PET. DISCUSSION: In this model simulation we show that the addition of PET to IUT reduces the severity of polycythemia in the recipient. PET may thus be important to prevent complications of hyperviscosity. CONCLUSION: This model simulation shows the beneficial effect of PET for the recipient in TAPS cases treated with IUT.

Perfusion territories subtended by penetrating coronary arteries increase in size and decrease in number toward the subendocardium.

Blood flow distribution within the myocardium and the location and extent of areas at risk in case of coronary artery disease are dependent on the distribution and morphology of intramural vascular crowns. Knowledge of the intramural vasculature is essential in novel multiscale and multiphysics modeling of the heart. For this study, eight canine hearts were analyzed with an imaging cryomicrotome, developed to acquire high-resolution spatial data on three-dimensional vascular structures. The obtained vasculature was skeletonized, and for each penetrating artery starting from the epicardium, the dependent vascular crown was defined. Three-dimensional Voronoi tessellation was applied with the end points of the terminal segments as center points. The centroid of end points in each branch allowed classification of the corresponding perfusion territories in subendocardial, midmyocardial, and subepicardial. Subendocardial regions have relatively few territories of about 0.5 ml in volume having their own penetrating artery at the epicardium, whereas the subepicardium is perfused by a multitude of small perfusion territories, in the order of 0.01 ml. Vascular volume density of small arteries up till 400 µm was 3.2% at the subendocardium territories but only 0.8% in the subepicardium territories. Their higher volume density corresponds to compensation for flow impeding forces by cardiac contraction. These density differences result in different scaling law properties of vascular volume and tissue mass per territory type. This novel three-dimensional quantitative analysis may form the basis for patient-specific computational models on coronary perfusion and aid the interpretation of image-based clinical methods for assessing the transmural perfusion distribution.

Quantification of feto-fetal transfusion rate through a single placental arterio-venous anastomosis in a monochorionic twin pregnancy.

Twin-to-twin transfusion syndrome (TTTS) is due to unbalanced inter-twin blood flow through placental vascular anastomoses. We present a TTTS-case treated with fetoscopic laser surgery that allowed us to calculate the net inter-twin blood flow. In the weeks following laser treatment, the ex-recipient developed severe fetal anemia and was treated with two intrauterine adult red cell transfusions (at 26 and 29 weeks' gestation, respectively). After birth, placental injection with color-latex identified a single residual arterio-venous anastomosis from the ex-recipient to the ex-donor. We measured the fetal and adult hemoglobin concentrations in the anemic fetus before and after both intrauterine transfusions, and in both twins at birth. On the basis of these measurements, we calculated the blood flow across the residual arterio-venous anastomosis and found it to be 5.8+/-1.5 mL/24h after the 1st transfusion and 11.4+/-2.9 mL/24h after the 2nd transfusion.

Placental characteristics of monoamniotic twin pregnancies in relation to perinatal outcome.

OBJECTIVE: To study placental characteristics in relation to perinatal outcome in 55 pairs of monochorionic monoamniotic (MA) twins. METHODS: Between January 1998 and May 2008 55 pairs of MA twins were delivered in 4 tertiary care centers and analysed for mortality, birth weight discordancy and twin-to-twin transfusion syndrome (TTTS) in relation to type of anastomoses, type and distance between cord insertions and placental sharing. Five acardiac twins, 2 conjoined twins, 4 higher order multiples and one early termination of pregnancy were excluded, leaving 43 MA placentas for analysis. Of these 43, one placenta could not be analysed for placental vascular anastomoses due to severe maceration after single intra-uterine demise leaving 42 placentas for analysis of anastomoses. RESULTS: Arterio-arterial (AA), venovenous (VV) and arteriovenous (AV) anastomoses were detected in 98%, 43% and 91% of MA placentas, respectively. Velamentous cord insertion was found in 4% of cases. Small distance between both umbilical cord insertions (<5 cm) was present in 53% of MA placentas. Overall perinatal loss rate was 22% (19/86). We found no association between mortality and type of anastomoses, type and distance between cord insertions and placental sharing. The incidence of TTTS was low (2%) and occurred in the only pregnancy with absent AA-anastomoses. CONCLUSION: Perinatal mortality in MA twins was not related to placental vascular anatomy. The almost ubiquitous presence of compensating AA-anastomoses in MA placentas appears to prevent occurrence of TTTS.

Simulated sequential laser therapy of twin-twin transfusion syndrome.

Sequential laser therapy of twin-twin transfusion syndrome (TTTS) includes laser obliteration of arteriovenous (AV) anastomoses from donor to recipient (AVDR) before obliterating AV anastomoses from recipient to donor (AVRD). This strategy allows for a beneficial intra-operative transfusion of blood from the hypervolemic recipient to the hypovolemic donor. In the present study, we sought to analyze the benefits and risks of sequential laser therapy with our computational model to aid its more widespread introduction. We simulated an equally shared placenta with an AVDR and a smaller diameter AVRD causing TTTS at 20 weeks. Laser coagulation and various volumes and directions of inter-twin transfusion were simulated at 21 weeks. A typical result is that when an AVDR is coagulated first, and 10 min later the AVRD with inner diameter of about 1 mm, an inter-twin transfusion of 25 ml may result from the recipient to the donor, based on literature data of AV flow versus diameter. This procedure causes a simulated loss of 50% of the recipient's blood volume. The opposite coagulation sequence, thus coagulating the AVRD first, 10 min later followed by the AVDR of 1 mm inner diameter, causes a loss of the donor's blood volume of 64%. In conclusion, our simulations support the concept of sequential laser therapy for TTTS and suggest directions for an improved safety and efficacy of this strategy.

Fetoscopic laser treatment of twin-to-twin transfusion syndrome followed by severe twin anemia-polycythemia sequence with spontaneous resolution.

We present a case of twin anemia-polycythemia sequence after laser surgery for twin-to-twin transfusion syndrome which resolved spontaneously. No residual anastomoses were identified after placental injection with colored dye. We discuss the possible pathogenetic mechanisms that may have led to this remarkable clinical course and discuss the various management options.

Case report: twin-to-twin transfusion syndrome resulting from placental collateral artery development.

BACKGROUND: The twin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies, caused by a net inter-twin transfusion of blood from one fetus (the donor) towards the other fetus (the recipient) through placental anastomoses. TTTS is driven by unidirectional arterio-venous anastomoses, and mitigated by bidirectional arterio-arterial or veno-venous anastomoses which reduce the net inter-twin transfusion. In contrast to these accepted concepts, cases have been described paradoxically devoid of arterio-venous anastomoses but including arterio-arterial anastomoses. We hypothesized that TTTS may develop in such cases as a consequence of a stenosed chorionic artery in the recipient placenta that connects with the arterio-arterial anastomosis. CLINICAL CASES: We describe two cases of monochorionic twin placentae without arterio-venous anastomoses but with only an arterio-arterial and veno-venous anastomosis. In one case severe TTTS developed. There, the arterio-arterial anastomosis connected to a stenosed chorionic artery in the recipient placenta and showed a tortuous appearance. The other case developed uneventful. It lacked a stenosed chorionic artery and the arterio-arterial anastomosis was non-tortuous. CONCLUSION: We present evidence that the arterio-arterial anastomosis represented a functional collateral artery whose outgrowth was driven by an increased shear-stress caused by an increased flow to a lower pressure vascular bed in the placenta of the recipient. The lower arterial pressure occurred from the moment that a chorionic artery which was connected to the anastomosis developed a significant stenosis. The resulting collateral flow through the anastomosis maintained blood supply to the lower pressure placental bed, the beneficial function of collaterals, but also resulted in an increasing net inter-twin transfusion which triggered onset of severe TTTS.

Regulation of amniotic fluid volume.

Water arrives in the mammalian gestation from the maternal circulation across the placenta. It then circulates between the fetal water compartments, including the fetal body compartments, the placenta and the amniotic fluid. Amniotic fluid is created by the flow of fluid from the fetal lung and bladder. A major pathway for amniotic fluid resorption is fetal swallowing; however, in many cases the amounts of fluid produced and absorbed do not balance. A second resorption pathway, the intramembranous pathway (across the amnion to the fetal circulation), has been proposed to explain the maintenance of normal amniotic fluid volume. Amniotic fluid volume is thus a function both of the amount of water transferred to the gestation across the placental membrane, and the flux of water across the amnion. Water flux across biologic membranes may be driven by osmotic or hydrostatic forces; existing data suggest that intramembranous flow in humans is driven by the osmotic difference between the amniotic fluid and the fetal serum. The driving force for placental flow is more controversial, and both forces may be in effect. The mechanism(s) responsible for regulating water flow to and from the amniotic fluid is unknown. In other parts of the body, notably the kidney, water flux is regulated by the expression of aquaporin water channels on the cell membrane. We hypothesize that aquaporins have a role in regulating water flux across both the amnion and the placenta, and present evidence in support of this theory. Current knowledge of gestational water flow is sufficient to allow prediction of fetal outcome when water flow is abnormal, as in twin-twin transfusion syndrome. Further insight into these mechanisms may allow novel treatments for amniotic fluid volume abnormalities with resultant improvement in clinical outcome.

Amniotic fluid water dynamics.

Water arrives in the mammalian gestation from the maternal circulation across the placenta. It then circulates between the fetal water compartments, including the fetal body compartments, the placenta and the amniotic fluid. Amniotic fluid is created by the flow of fluid from the fetal lung and bladder. A major pathway for amniotic fluid resorption is fetal swallowing; however in many cases the amounts of fluid produced and absorbed do not balance. A second resorption pathway, the intramembranous pathway (across the amnion to the fetal circulation), has been proposed to explain the maintenance of normal amniotic fluid volume. Amniotic fluid volume is thus a function both of the amount of water transferred to the gestation across the placental membrane, and the flux of water across the amnion. Membrane water flux is a function of the water permeability of the membrane; available data suggests that the amnion is the structure limiting intramembranous water flow. In the placenta, the syncytiotrophoblast is likely to be responsible for limiting water flow across the placenta. In human tissues, placental trophoblast membrane permeability increases with gestational age, suggesting a mechanism for the increased water flow necessary in late gestation. Membrane water flow can be driven by both hydrostatic and osmotic forces. Changes in both osmotic/oncotic and hydrostatic forces in the placenta my alter maternal-fetal water flow. A normal amniotic fluid volume is critical for normal fetal growth and development. The study of amniotic fluid volume regulation may yield important insights into the mechanisms used by the fetus to maintain water homeostasis. Knowledge of these mechanisms may allow novel treatments for amniotic fluid volume abnormalities with resultant improvement in clinical outcome.

Significance of donor anuria differs between monoamniotic and diamniotic twin-twin transfusion syndrome.

Development of severe twin-twin transfusion syndrome (TTTS) in diamniotic-monochorionic twins includes five stages of increasing severity, i.e. recipient polyhydramnios and donor oligohydramnios, donor anuria, abnormal umbilical flow velocities in either twin, hydrops in the recipient, and intrauterine fetal death (IUFD) in either or both twins. In a severe case of TTTS in monoamniotic twins we observed donor anuria to appear after hydrops in the recipient. We conclude that donor anuria is a late and serious symptom in monoamniotic TTTS.

Assessment of feto-fetal transfusion flow through placental arterio-venous anastomoses in a unique case of twin-to-twin transfusion syndrome.

In vivo measurements of blood flow through arterio-venous anastomoses in monochorionic twin placentas have recently been attempted with Doppler ultrasound, but the accuracy is questionable. We present a case of twin-to-twin transfusion syndrome treated with fetoscopic laser surgery. The ex-recipient subsequently became severely anaemic and was treated with an intrauterine blood transfusion at 29 weeks' gestation. After birth, a placental injection study identified residual unidirectional arterio-venous anastomoses from the ex-recipient to the ex-donor without arterio-venous anastomoses in the opposite direction. Prospective measurements of decreasing haemoglobin levels between the intrauterine transfusion and birth allowed us to assess the net blood flow through the anastomoses as 27.9mL/24h. This finding may also explain the inaccuracy of Doppler flow measurements, as such low flow velocities cannot possibly be detected with current Doppler techniques.

Colour oscillations in arterioarterial anastomoses reflect natural differences in donor and recipient oxygenation and hematocrit.

Our aim was to show that the colour difference between brighter and darker red, occasionally observed as an oscillating boundary in the recipient and donor parts of an arterioarterial anastomosis in severe twin-twin transfusion syndrome (TTTS), is a consequence of natural differences in blood oxygenation and hematocrit developing between donor and recipient twins. As method we defined a theoretical model of the placenta with dimensions from pathology examination. From literature we determined the optical absorption and scattering properties of all tissue components, and hematocrit and oxygen saturation values for donor and recipient twins. From our placental model we simulated the spectrum of back-scattered light by standard Monte Carlo photon propagation computations and calculated the colour of chorionic arterial and venous blood vessels by applying the physics theory of colour perception. Our computations demonstrate that recipient arterial blood is somewhat brighter red than donor arterial blood. The strong colour differences seen after laser coagulation of all anastomoses but the arterioarterial were explained from an angiotensin II cut-off in the recipient due to obliteration of arteriovenous anastomoses, causing a temporary increase in recipient placental perfusion and hence in blood oxygenation. In conclusion, natural differences in recipient versus donor blood oxygen saturation and hematocrit in severe TTTS explain the observed colour differences between brighter and darker red observed in the recipient and donor parts of arterioarterial anastomoses.