Direction Of Blood Flow Research Articles

A Preliminary Study on the Functionality of the Carotid-Vertebral Anastomotic Artery in the Regulation of Blood Flow in the Giraffe (Giraffa camelopardalis) by Duplex Ultrasound Examination

Postural change intermittently between upright and head down in giraffes standing at a height of 4.5 meters is of physiological significance. The length of a giraffe’s neck denotes the flow of blood against the force of gravity, to supply the brain over a 2 m distance. The force of gravity also affects the flow of blood toward the brain, with a posture change from erect to ground level. How do these changes in stance not result in fainting when the head is raised and brain damage when the head is lowered? Giraffe has an advanced interconnection of the common carotid artery and the vertebral artery. The connection is located at the midpoint of the atlas, as indicated by means of computerized tomography and dissection. Duplex ultrasound with Doppler waveform examination showed the unidirectional movement of blood with movement from the vertebral artery into the common carotid artery when the head is erect. The direction of flow allows the provision of blood to the maxillary artery that feeds the rostral epidural rete that supplies to the brain. The flow direction in the carotid-vertebral connection changes when blood moves in the direction of the head along with the force of gravity, when the head is lowered. The rerouting of blood to move from the common carotid into the vertebral artery prevents brain damage. We have confirmed, by utilizing a CT scan, Doppler sonar, and dissection of latex-filled arteries, the existence and blood flow direction within the anastomotic artery associated with variation in posture in the giraffe.

Automatic boundary detection and severity assessment of mitral regurgitation

The most prevalent disease, cardiovascular disease (CVD), has a high mortality rate among people. The prognosis of CVD depends on early diagnosis. In the event of any abnormality, such as valvular regurgitation and stenosis, the blood flow patterns, direction, and velocity are detected using the color Doppler echocardiography. Today’s clinicians determine the regurgitant jet region manually in the echocardiographic images with the aid of a cursor to assess the severity of mitral regurgitation (MR). Manual tracing takes a lot of time and involves both intra and inter-personal variances. This research offers an automatic delineation technique to quantify the regurgitant jet area value to address this problem. The level of MR severity, specifically mild, moderate, and severe, is then connected to the analyzed jet area. The suggested approach combines various segmentation methods, such as color space model, thresholding, and morphological operators, for segmenting echocardiographic pictures. A total of 75 MR-related images from 25 individuals have been evaluated. In light of the regurgitant jet area identified by the suggested technique and contrasted with the manual way of MR assessment, the severity of MR has been assessed. The segmentation procedure can be segmented to remove the imitation areas using the established method. The regurgitant jet region collected using the suggested technique satisfies the clinical objectives in the quick evaluation of MR severity.

Comparative evaluation of straight and curved extension dialysis catheters for continuous renal replacement therapy in dogs with acute kidney injury.

A patent dual-lumen dialysis catheter is one of the basic requirements for efficient extracorporeal (EC) therapy. The objective of this study was to measure the resistance to blood flow offered by straight and curved-extension dual-lumen dialysis catheters used for continuous renal replacement therapy (CRRT). Twenty dogs suffering from acute kidney injury (AKI) were subjected to CRRT. The dogs were allocated randomly to Group-I (curved extension catheter, n=12) or Group II (straight extension catheter, n=8), based on the type of dual-lumen catheter used in CRRT. The catheter outflow and inflow pressures were recorded at blood pump speeds of 50 ml/min and 99-100 ml/min. Data were tested for normality, and differences in mean inflow and outflow catheter resistances were evaluated for statistical significance using independent samples t-tests. Straight extension catheters offered lower inflow resistance than curved extension catheters at both 50 ml/min (41.50 ± 5.84 mm Hg vs. 63.75 ± 6.88 mm Hg, P=0.03) and 99-100 ml/min (63.00 ± 8.11 mm Hg vs. 86.92 ± 7.02 mm Hg, P=0.04) blood flow rates. Straight extension catheters also offered lower outflow resistance than curved catheters at 99-100 ml/min blood flow rate (-94.12 ± 7.91 mm Hg vs. -128.25 ± 7.56 mm Hg, P=0.01; the negative signs only indicate the direction of blood flow). These findings suggest that straight-extension dual-lumen dialysis catheters perform better than the curved model in extracorporeal renal replacement therapy by considering their lower resistance to blood flow.

Construction of a canine model with acute type B aortic dissection using a self-made pressure-driven flow device.

A reproducible canine aortic dissection (AD) model would be useful for evaluating the performance of novel endovascular treatment devices. Therefore, we attempted to create a reproducible canine model of Stanford type B AD (TBAB) by a surgical method. Computed tomography angiography was performed 2 h after the procedure to determine if a false lumen was present, and follow-up imaging was performed 10 d after the procedure using digital subtraction angiography, intravascular ultrasound (IVUS), and color Doppler flow imaging (CDFI) to confirm stable persistence of the false lumen. The success rate of model construction was 88.8% (16/18). All surviving dogs had distal re-entries (16/16). The number of re-entries in the dogs was 1.50 ± 0.52, and the mean length of the false lumen was 175.37 ± 16.98 mm. IVUS showed the area of the false lumen at the narrowest part of the arterial lumen was 84.88 ± 1.27%. The CDFI showed that the peak systolic velocity in the false lumen (10.89 ± 0.74 cm/s) was significantly slower than that in the true lumen (25.31 ± 1.72 cm/s; P<0.001). Moreover, the direction of blood flow in the true lumen was consistent, whereas that in the false lumen was disordered. We optimized the traditional surgical method to construct a canine model of TBAD to improve the success rate of model construction, and designed a novel device to lengthen the false lumen. The proposed model has wide implications in evaluating the performance of novel endovascular treatment devices and studying the AD-related hemodynamics.

Development of a perfusable, hierarchical microvasculature-on-a-chip model.

Several methods have been developed for generating 3D, in vitro, organ-on-chip models of human vasculature to study vascular function, transport, and tissue engineering. However, many of these existing models lack the hierarchical nature of the arterial-to-capillary-to-venous architecture that is key to capturing a more comprehensive view of the human microvasculature. Here, we present a perfusable, multi-compartmental model that recapitulates the three microvascular compartments to assess various physiological properties such as vessel permeability, vasoconstriction dynamics, and circulating cell arrest and extravasation. Viscous finger patterning and passive pumping create the larger arterial and venular lumens, while the smaller diameter capillary bed vessels are generated through self-assembly. These compartments anastomose and form a perfusable, hierarchical system that portrays the directionality of blood flow through the microvasculature. The addition of collagen channels reduces the apparent permeability of the central capillary region, likely by reducing leakage from the side channels, enabling more accurate measurements of vascular permeability-an important motivation for this study. Furthermore, the model permits modulation of fluid flow and shear stress conditions throughout the system by using hydrostatic pressure heads to apply pressure differentials across either the arteriole or the capillary. This is a pertinent system for modeling circulating tumor or T cell dissemination and extravasation. Circulating cells were found to arrest in areas conducive to physical trapping or areas with the least amount of shear stress, consistent with hemodynamic or mechanical theories of metastasis. Overall, this model captures more features of human microvascular beds and is capable of testing a broad variety of hypotheses.

The Direction of Flow and Phase-encoding Schemes Effects on Signal Intensity in T1-weighted Inversion Recovery TurboFLASH Images.

It is needed to minimize the effect of flow direction on the desired area, such as arterial input function (AIF) in magnetic resonance imaging (MRI). The current study aimed to investigate the effect of flow direction on different velocities (0-80.39 cm/s) for the strength of the signal intensity (SI) at the linear phase-encoding (LPE) and the center out phase-encoding (COPE) schemes and to recommend the best flow direction in a selected slice and scheme for absolute perfusion measurement by inversion recovery T1-weighted turbo fast low-angle shot (TurboFLASH) MR images. In this experimental study, the flow rates were measured using a flow phantom, and the signal intensity (SI) was measured at the two opposite flow directions in the Z-axis perpendicular to the coronal image at a concentration of 0.8 mmol/L of gadolinium-diethylenetriaminepantaacetic acid (Gd-DTPA) by using the LPE and COPE schemes. The increase in velocity along with the growth in SI and inflow affected the use of LPE and COPE acquisitions in both directions. The velocity of the arterial input function is needed to calculate the inflow correction factor by using two schemes in two opposite flow directions to investigate perfusion. The COPE scheme was better than the LPE scheme in measuring perfusion since the velocity and direction of blood flow affect SI less.

Compensation pathways for venous drainage of the brain in superior sagittal sinus occlusion by parasagittal meningioma

This study aims to determine the existing pathways of collateral cerebral circulation in parasagittal meningiomas that cause superior sagittal sinus occlusion based on literature review and analysis of own clinical observations. Results of clinical and instrumental examination of 221 patients treated in Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov from 2000 to 2021 were subjected to retrospective and prospective analysis. Inclusion criteria were: patient age of 18+, parasagittal extracerebral tumor according to computed tomography/magnetic resonance imaging, histologically verified meningioma, superior sagittal sinus occlusion (type V-VI according to M.P. Sindou and J.E. Alvernia) according to selective cerebral angiography. This study is based on the analysis of examination of 43 patients who met the inclusion criteria. The selected patients were analyzed for demography (sex, age), brain computed tomography/magnetic resonance imaging before and after intravenous contrast enhancement, and computed tomography angiography and selective cerebral angiography data. Transformed venous drainage pathways were analyzed depending on the location of superior sagittal sinus occlusion by parasagittal meningioma: anterior, middle, or posterior third of the superior sagittal sinus. It was determined that preoperative diagnosis of parasagittal meningiomas that, based on brain computed tomography/magnetic resonance imaging, has signs of type V or VI superior sagittal sinus invasion according M.P. Sindou and J.E. Alvernia, must include selective cerebral angiography. Dynamic images of selective cerebral angiography in the venous phase allows to fully assess the established pathways of collateral blood flow and the blood flow direction. Information on collateral venous circulation in case of superior sagittal sinus occlusion by parasagittal meningioma is extremely important in a surgery planning. It helps avoiding iatrogenic damage to eloquent veins, which increases radical tumor removal with maintaining/improving a patient’s functional state in the early postoperative period and improving long-term treatment outcomes.

Novel Use of Time-Resolved Magnetic Resonance Angiography to Evaluate Retrograde Lumbar Vein Flow and Epidural Venous Plexus Enhancement in Chronic Headache Patients With and Without Nutcracker Physiology.

Compression of the left renal vein by the superior mesenteric artery, known as nutcracker phenomenon (NCP), can cause retrograde flow and congestion in communicating venous systems. It has recently been speculated that NCP can result in retrograde flow and congestion of the lumbar veins and epidural venous plexus (EVP), thereby affecting the central nervous system. This study describes the novel use of time-resolved magnetic resonance angiography (trMRA) to evaluate for retrograde left second lumbar vein (L2LV) flow and early EVP enhancement in patients with chronic daily headache (CDH) with and without NCP. A retrospective analysis was performed of 31 patients with CDH (27 females and 4 males; median age, 38 years [range, 18-63 years]) who underwent trMRA centered over the L2LV to evaluate the direction of blood flow and presence of early EVP enhancement from May 2020 to March 2022. Descriptive statistics were performed, and anatomic associations were analyzed in patients with and without retrograde L2LV flow and early EVP enhancement. The accuracy of magnetic resonance imaging findings in detecting these flow patterns was also assessed. Patients with NCP who demonstrated narrowing of the left renal vein, a positive beak sign ( P = 0.052), decreased aortomesenteric distance ( P = 0.038), and decreased SMA angle demonstrated increased rates of retrograde L2LV flow and early EVP enhancement. A positive beak sign was 83% specific, and an aortomesenteric distance of ≤6.5 mm was 61% sensitive and 83% specific for identifying retrograde L2LV flow with early regional EVP enhancement in patients with CDH. Retrograde L2LV flow with early EVP enhancement in CDH patients can be effectively evaluated using trMRA and was seen with greater propensity in those patients with NCP.

Tailup expression in Drosophila larval and adult cardiac valve cells.

In Drosophila larvae, the direction of blood flow within the heart tube, as well as the diastolic filling of the posterior heart chamber, is regulated by a single cardiac valve. This valve is sufficient to close the heart tube at the junction of the ventricle and the aorta and is formed by only two cells; both are integral parts of the heart tube. The valve cells regulate hemolymph flow by oscillating between a spherical and a flattened cell shape during heartbeats. At the spherical stage, the opposing valve cells close the heart lumen. The dynamic cell shape changes of valve cells are supported by a dense, criss-cross orientation of myofibrils and the presence of the valvosomal compartment, a large intracellular cavity. Both structures are essential for the valve cells' function. In a screen for factors specifically expressed in cardiac valve cells, we identified the transcription factor Tailup. Knockdown of tailup causes abnormal orientation and differentiation of cardiac muscle fibers in the larval aorta and inhibits the formation of the ventral longitudinal muscle layer located underneath the heart tube in the adult fly and affects myofibrillar orientation of valve cells. Furthermore, we have identified regulatory sequences of tup that control the expression of tailup in the larval and adult valve cells.

416 DESMOPLAKIN CARDIOMYOPATHY PRESENTING WITH CARDIAC ARREST IN A PATIENT WITH MYOCARDIAL NON-COMPACTION AND LEFT ACCESSORY PATHWAY

Abstract Introduction Desmoplakin is a human protein which plays a key role into desmosomes structure. Desmoplakin gene mutations can cause the so-called "desmoplakin cardiomyopathy", a form of arrhythmogenic cardiomyopathy. Its clinical history is characterized by severe ventricular arrhythmias, episodic myocardial injury and left ventricular systolic dysfunction associated with fibrosis. Case Presentation A 12-years-old male came to our inherited cardiomyopathy ambulatory for cardiological evaluation due to a previous history of cardiac arrest when he was infant (30 days newborn) and palpitation. Previous medical history included eczematous dermatitis and occasional hyperglycemia. During cardiological evaluation EKG was unremarkable, echocardiography revealed myocardial noncompaction in apical and mid-ventricular regions of the left ventricle's infero-lateral wall (end systolic ratio 2:1) and evidence of direct blood flow into deep intertrabecular recesses by colour doppler. Due to history of palpitation an EP study was performed that showed a lateral left-sided accessory pathway that was ablated during the same procedure. A genetic molecular analysis with exome sequencing (NGS, next generation sequencing) was performed and revealed a heterozygous genetic variant in DSP (Desmoplakin) gene on chromosome 6 (c.4046 G&amp;gt;A pSer1349Asn). Familiar screening revealed the same genetic variant in his father and his brother, both had no cardiological events. Conclusion Desmoplakin cardiomyopathy may have a severe clinical presentation with cardiac arrest. A multidisciplinary approach is suggested for a tailored management of these patients.

Temporary Reversal of Hepatoenteric Collaterals during 90Y Radioembolization Planning and Administration

This paper aims to evaluate the safety and efficacy of the temporary redirection of blood flow of hepatoenteric collaterals using a balloon catheter in the common hepatic artery (CHA) to prevent the nontarget deposition of 90Y microspheres. In this retrospective single-center study of patients who received 90Y radioembolization (RE) from September 2010 to September 2015, diagnostic (67 patients) or treatment (72 patients) angiograms with the attempted use of a balloon catheter in the CHA to temporarily direct blood flow away from the hepatoenteric arteries were analyzed. SPECT/CT nuclear scintigraphy was performed after both diagnosis and treatment. Overall, only 12 hepatoenteric arteries in 11 patients required embolization due to persistent hepatoenteric flow despite the use of the balloon occlusion technique in a total of 86 patients. Physicians performed the 90Y RE using balloon occlusion with glass (n = 22) or resin (n = 50) microspheres. Over 80% administration of the prescribed 90Y dose was accomplished in 34 (67%) resin and 20 (95%) glass microsphere patients. Post-treatment 90Y RE scintigraphy confirmed the absence of extrahepatic activity in all patients. One grade 2 gastrointestinal ulcer was present after 90 days of follow-up. Temporary CHA occlusion with a balloon catheter is a reliable and reproducible alternative to the conventional coil embolization of hepatoenteric arteries during diagnostic Tc-99m macroaggregated albumin and therapeutic 90Y RE delivery.

On-chip spectroscopic monitoring of erythrocyte oxygenation under hematocrit and oxygen gradients

The interpretation of the variability and determinants of erythrocyte oxygenation is complicated by multiple interacting factors manifesting gaseous and fluidic microenvironments during microcirculation. In this paper, a multifunctional microdevice was developed for quantitatively extracting the dominant role of RBC concentration, local oxygen (O 2 ), and fluid dynamics in an ex vivo setting. Serial dilution of RBCs was achieved by repeated splitting and mixing of the source RBC suspension solutions in the bifurcating serpentine microchannels. O 2 perfusion of buried microchannels in a gas-permeable polydimethylsiloxane membrane allowed for exposing RBCs to a spatial linear O 2 gradient along with the blood flow direction. Taking the variability in the optically relevant properties of erythrocytes and their oxygenation status, an optical-fiber-based measurement system was integrated with the microfluidic device to capture the characteristic spectroscopic features of RBCs covering the visible to near-infrared range. The spectroscopic analysis provided a linear regression model of oxygen saturation with variables containing RBC concentrations, O 2 levels, and blood flow velocity, which agreed well with numerical simulation results. This systematic experimental approach could be applicable as an in vitro microcirculatory model system while adding a dimension to a wide range of blood processing and analysis. • A microfluidic device was developed for rendering serial RBC and O 2 gradients. • The vis-NIR spectra of RBCs were captured by an on-chip optical-fiber system. • The RBC oxygenation was studied with multiple variables and increased throughput. • Numerical simulation and vis-NIR spectra analysis showed a consistent StO 2 profile.

Novel hybrid total artificial heart with integrated oxygenator.

There continues to be an unmet therapeutic need for an alternative treatment strategy for respiratory distress and lung disease. We are developing a portable cardiopulmonary support system that integrates an implantable oxygenator with a hybrid, dual-support, continuous-flow total artificial heart (TAH). The TAH has a centrifugal flow pump that is rotating about an axial flow pump. By attaching the hollow fiber bundle of the oxygenator to the base of the TAH, we establish a new cardiopulmonary support technology that permits a patient to be ambulatory during usage. In this study, we investigated the design and improvement of the blood flow pathway from the inflow-to-outflow of four oxygenators using a mathematical model and computational fluid dynamics (CFD). Pressure loss and gas transport through diffusion were examined to assess oxygenator design. The oxygenator designs led to a resistance-driven pressure loss range of less than 35 mmHg for flow rates of 1-7 L/min. All of the designs met requirements. The configuration having an outside-to-inside blood flow direction was found to have higher oxygen transport. Based on this advantageous flow direction, two designs (Model 1 and 3) were then integrated with the axial-flow impeller of the TAH for simulation. Flow rates of 1-7 L/min and speeds of 10,000-16,000 RPM were analyzed. Blood damage studies were performed, and Model 1 demonstrated the lowest potential for hemolysis. Future work will focus on developing and testing a physical prototype for integration into the new cardiopulmonary assist system.

Slow flow induces endothelial dysfunction by regulating thioredoxin-interacting protein-mediated oxidative metabolism and vascular inflammation.

Endothelial cells are highly sensitive to hemodynamic shear stresses, which act in the blood flow's direction on the blood vessel's luminal surface. Thus, endothelial cells on that surface are exposed to various physiological and pathological stimuli, such as disturbed flow-induced shear stress, which may exert effects on adaptive vascular diameter or structural wall remodeling. Here we showed that plasma thioredoxin-interactive protein (TXNIP) and malondialdehyde levels were significantly increased in patients with slow coronary flow. In addition, human endothelial cells exposed to disturbed flow exhibited increased levels of TXNIP in vitro. On the other hand, deletion of human endothelial TXNIP increased capillary formation, nitric oxide production and mitochondrial function, as well as lessened oxidative stress response and endothelial cell inflammation. Additional beneficial impacts from TXNIP deletion were also seen in a glucose utilization study, as reflected by augmented glucose uptake, lactate secretion and extracellular acidification rate. Taken together, our results suggested that TXNIP is a key component involved in mediating shear stress-induced inflammation, energy homeostasis, and glucose utilization, and that TXNIP may serve as a potentially novel endothelial dysfunction regulator.

Abstract 231: Volume And Direction Of Carotid Blood Flow During Cardiopulmonary Resuscitation In A Porcine Model Of Ventricular Fibrillation

Introduction: Hemodynamics during cardiopulmonary resuscitation (CPR) is not well understood. We aimed to quantitatively evaluate the volume and direction of carotid blood flow (CBF) during CPR in a porcine model of ventricular fibrillation (VF) cardiac arrest. Methods: Nineteen male domestic pigs were intubated and ventilated mechanically. Following baseline measurements, VF was electrically induced. CBF was measured continuously using a flow probe positioned around the common carotid arteries. After 0 or 5 min no-flow time of untreated VF, CPR was initiated, involving chest compressions and ventilation with oxygen. CPR was continued for 25 min, with mechanical (L1, L2, and L3) and manual (M1 and M2) CPR alternated at 5 min intervals. A Friedman test was used to compare the groups in each phase. Post hoc analysis was performed using a Wilcoxon signed-rank test (Bonferroni corrected). Results: CBF was calculated as the average of each phase. The net flow was calculated through subtracting the retrograde flow from the anterograde flow. Average net flow (median, interquartile range [IQR], mL/min) during CPR was 58.1 (24.0-111.3), 19.8 (8.4-24.9), 21.2 (9.5-37.9), 15.4 (8.4-24.9), and 16.4 (10.3-30.1) in phases L1, M1, L2, M2, and L3, respectively ( p &lt; 0.001, L1 vs. M1). The ratio (median, IQR, %) of retrograde to anterograde flow was 41.3 (16.7-58.7), 48.6 (33.1-60.4), 42.2 (36.5-76.4), 49.1 (39.4-68.5), and 50.0 (38.0-79.0) in phases L1, M1, L2, M2, and L3, respectively ( p = 0.299). Conclusions: In this VF cardiac arrest model, the net flow of the carotid artery during CPR decreased with time. Both mechanical and manual CPR produced substantial retrograde flow, although the ratio of retrograde to anterograde flow did not change.

PMON108 Metastatic Prostate Cancer Presenting as a Pituitary Macroadenoma: A Case Report

Abstract Introduction Prostate cancer is the most common non-skin malignancy with an increasing incidence of distant stage spread. Prostate cancer is most frequently associated with skeletal, lymph node, and pulmonary metastases. Intracranial metastases are rare, occurring in only 0.4-0.6 percent of all cases. However, silent pituitary metastases are not uncommon in autopsy reports of cancer patients, with breast and lung cancer being the most common primary origin. Here we report a rare case of metastatic prostate adenocarcinoma that was originally thought to be a pituitary macroadenoma. Clinical Case A 57-year-old male with no known history of malignancy who presented with two weeks of headaches exacerbated by leaning forward. MRI showed a 2.8×2.8×2.7 cm sellar/suprasellar mass extending into the clivus and right sphenoid sinus favored to reflect a pituitary macroadenoma. He was found to have no visual, neurological, or endocrine abnormalities on exam, in addition to normal laboratory evaluation. He subsequently underwent transnasal resection of the mass and pathology revealed metastatic prostate cancer. Postoperative studies also revealed a significantly elevated prostate specific antigen (PSA) level of 383.8 ng/mL (normal range 0-4ng/mL) and a left posterolateral prostate mass extending into the left seminal vesicle, as well as multiple osseous metastases. In retrospect, he had been found to have an elevated PSA of 49.5 ng/mL five months prior which was thought to be secondary to infection but had not yet been repeated by his primary care provider. Fortunately, he had a favorable response to androgen deprivation therapy and Abiraterone/Prednisone. His PSA level decreased to &amp;lt;0.1 ng/mL and MRI showed complete resolution of the sellar/suprasellar mass while on androgen deprivation therapy. Discussion The rarity of pituitary metastases as well as lack of specific clinical and radiological features can make it difficult to differentiate from the much more common benign pituitary adenoma. Pituitary metastases are frequently asymptomatic or can present similarly to pituitary adenomas with headaches, visual changes, or hypopituitarism. Posterior pituitary metastases have been more frequently reported than anterior, thought to be due to the larger area of contact with the adjacent dura and direct blood flow from the systemic circulation. Rapid progression of size and symptoms, age greater than 50, and presence of diabetes insipidus should all raise suspicion for pituitary metastases, regardless of oncologic history, as the differentiation between malignant and benign is imperative in determining a therapeutic plan. The overall prognosis is poor in patients with prostate cancer metastatic to the brain, with a reported mean survival of 1-3 months in untreated cases and up to 14 months in those who underwent surgery or radiotherapy. Conclusion This case reminds us of the importance of keeping malignant metastases in the differential diagnosis of sellar masses. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Super-Resolution Ultrasound Localization Microscopy of Microvascular Structure and Flow for Distinguishing Metastatic Lymph Nodes - An Initial Human Study.

Detecting and distinguishing metastatic lymph nodes (LNs) from those with benign lymphadenopathy are crucial for cancer diagnosis and prognosis but remain a clinical challenge. A recent advance in super-resolution ultrasound (SRUS) through localizing individual microbubbles has broken the diffraction limit and tracking enabled in vivo noninvasive imaging of vascular morphology and flow dynamics at a microscopic level. In this study we hypothesize that SRUS enables quantitative markers to distinguish metastatic LNs from benign ones in patients with lymphadenopathy. Clinical contrast-enhanced ultrasound image sequences of LNs from 6 patients with lymph node metastasis and 4 with benign lymphadenopathy were acquired and motion-corrected. These were then used to generate super-resolution microvascular images and super-resolved velocity maps. From these SRUS images, morphological and functional measures were obtained including micro-vessel density, fractal dimension, mean flow speed, and Local Flow Direction Irregularity (LFDI) measuring the variance in local flow direction. These measures were compared between pathologically proven reactive and metastasis LNs. Our initial results indicate that the difference in the indicator of flow irregularity (LFDI) derived from the SRUS images is statistically significant between the two groups. The LFDI is 60% higher in metastatic LNs compared with reactive nodes. This pilot study demonstrates the feasibility of super-resolution ultrasound for clinical imaging of lymph nodes and the potential of using the irregularity of local blood flow directions afforded by SRUS for the characterization of LNs.

CMR derived left ventricular intraventricular pressure gradients identify different patterns associated with prognosis in patients with dilated cardiomyopathy

Abstract Introduction The direction of blood flow in the left ventricle (LV) is determined by intraventricular pressure gradients (IVPGs) between apex and base, which are altered when cardiac function declines. New cardiac magnetic resonance (CMR) post-processing software enables estimating LV-IVPGs. To date, the prognostic value of CMR derived IVPGs in patients with dilated cardiomyopathy (DCM) remains unknown. Methods DCM patients from the Maastricht Cardiomyopathy Registry, who underwent a CMR, were included. The software estimates the LV-IVPGs (between apex and base) by using the myocardial movement and velocity of a reconstructed 3D-LV model (derived from feature-tracking strain analysis of 2-, 3- and 4-chamber cine images). The primary outcome was a combined endpoint of heart failure (HF) hospitalisations, life-threatening arrhythmias and (sudden) cardiac death. Results In total, 447 DCM patients were included (age 55 interquartile range [46–63] years; 60% male). During a median follow-up of 6 [4–9] years, 66 patients (15%) reached the primary endpoint. In 168 patients (38%), a temporary pressure reversal from base-apex to apex-base during the systolic-diastolic transition was observed (figure). After correction for covariates that were univariably associated with outcome (p&amp;lt;0.100, age, NYHA-class≥3, and left atrial (LA) conduit strain), flow reversal from base-apex to apex-base in the diastole was independently associated with outcome in the total cohort (HR 2.91, 95%-Confidence interval (95%-CI) [1.16–7.32], p=0.023; Table). In patients without pressure reversal (N=279) in the systolic-diastolic transition, IVPG during the total cardiac cycle (HR 0.88 [0.81–0.96], p=0.003), the systolic ejection force (HR 0.92 [0.87–0.97], p=0.003), and the E-wave decelerative force “C” (passive diastolic filling, HR 0.85 [0.74–0.97], p=0.013) were predictors of outcome, independent of other covariates (age, sex, NYHA class ≥3, LV ejection fraction, late gadolinium enhancement, LV longitudinal strain, LA volume index and LA conduit strain, table). Conclusion CMR-derived LV-IVPG analysis showed pressure reversal in the systolic-diastolic transition in one-third of DCM patients, and flow reversal was an independent predictor of worse outcome in these patients. In patients without this pressure reversal, LV-IVPG during the total cardiac cyle, the systolic ejection force, and the E-wave decelerative force were predictors of outcome, independent of all evauluated clinical and imaging parameters. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Netherlands Cardiovascular Research Initiative (initiative with support of the Dutch Heart Foundation) and CVON (She-PREDICTS, grant 2017-21 &amp; CVON-DCVA Double Dosis 2021)

A single-cell transcriptomic inventory of murine smooth muscle cells.

Smooth muscle cells (SMCs) execute important physiological functions in numerous vital organ systems, including the vascular, gastrointestinal, respiratory, and urogenital tracts. SMC differ morphologically and functionally at these different anatomical locations, but the molecular underpinnings of the differences remain poorly understood. Here, using deep single-cell RNA sequencing combined with in situ gene and protein expression analysis in four murine organs-heart, aorta, lung, and colon-we identify a molecular basis for high-level differences among vascular, visceral, and airway SMC, as well as more subtle differences between, for example, SMC in elastic and muscular arteries and zonation of elastic artery SMC along the direction of blood flow. Arterial SMC exhibit extensive organotypic heterogeneity, whereas venous SMC are similar across organs. We further identify a specific SMC subtype within the pulmonary vasculature. This comparative SMC cross-organ resource offers insight into SMC subtypes and their specific functions.

Assessment of Cerebrovascular Reserve in the Setting of Moyamoya Disease Using Arterial Spin-Labeling and Acetazolamide Challenge

Arterial spin-labeling is a safe, noninvasive, contrast-free MR imaging technique that can be used to assess CBF. In this review, we will briefly discuss the advantages and disadvantages of arterial spin-labeling juxtaposed to previously established modalities of cerebral perfusion imaging, summarize the materials and methods required for arterial spin-labeling, and provide clinical case examples in which application of arterial spin-labeling combined with an acetazolamide challenge was used safely to improve patient outcomes in the setting of Moyamoya disease. Arterial spin-labeling takes advantage of the directionality of arterial blood flow by labeling the patient's own endogenous water within the neck via radiofrequency pulse and imaging of the downstream brain after an appropriate delay. This tool allows repeatable intra- and intersession estimation of CBF to better assess postinterventional outcomes in patients with cerebrovascular dysfunction. One specific example of the utility of arterial spin-labeling is its application in patients with Moyamoya disease by selection and stratification of those most likely to benefit from surgical intervention. The combination of arterial spin-labeling with acetazolamide challenge is an effective way to assess cerebrovascular reserve in Moyamoya disease and is easily adaptable on a clinical 3T MR imaging scanner using a commercially available arterial spin-labeling pulse sequence to generate augmentation and steal maps. The entire study can be completed in only 20 minutes in a routine clinical setting.Learning Objective: To describe the implementation and interpretation of arterial spin-labeling combined with an acetazolamide challenge