Blood Transit Time Research Articles

7484 Pseudohypoglycemia In A Patient With Raynaud’s Phenomenon

Abstract Disclosure: J. Fedorko: None. P. Subarajan: None. A.P. Amblee: None. C.A. Poku: None. Background: The term ‘pseudohypoglycemia’ is used to describe the disparity between actual and measured capillary glucose and clinical presentation. It has been used to describe situations when a patient has the characteristic symptoms of low blood glucose (BG) Whipple’s triad), but the patient’s BG levels are within normal limits. Alternatively, this term can also be used to describe falsely low BG levels on finger-stick (capillary) readings in a patient with normal serum glucose levels and without the characteristic Whipple’s triad. Case: A 55-year-old female with Raynaud’s phenomenon was seen in Endocrine clinic with persistent hypoglycemia noted on finger-stick glucose readings. Her finger-stick glucose reading was 43, and was subsequently given 24 grams of glucose gel. Ten minutes later, a repeat finger stick BG was 44. She had no weakness, tremors, shakiness, vision changes, confusion, seizures, lightheadedness, dizziness, tachycardia, palpitations, nervousness, hunger, paresthesias irritability, confusion, seizures, loss of consciousness, or any other symptoms or signs of hypoglycemia. She had no such previous episodes and her fasting BG ranged from mid-70s to 80, with post-meal BG ranging from 100 to mid-100’s. Her most recent hemoglobin A1c was 5.5. She regularly experiences cyanosis of fingers consistent with Raynaud’s phenomenon, triggered by cold air in winter and air conditioners in summer. She does not take any medications for these episodes. Given the absence of classic Whipple triad and normal BG from peripheral blood draw, the patient’s low finger stick BG readings were attributable to Raynaud’s phenomenon. It is postulated to be secondary to decreased perfusion in the digital microcirculation and increased blood transit time in the fingers, resulting in a local increase in glucose consumption and thus low capillary finger stick BG levels. Simultaneously done serum glucose levels are usually normal. Conclusion: Pseudohypoglycemia can occur in patients with impaired peripheral circulation such as Raynaud’s phenomenon, acrocyanosis, peripheral vascular disease, shock, or with increased glycolysis by blood cells like in leukemia, polycythemia and rare infections like African trypanosomiasis, hyperviscosity syndromes like Waldenstrom’s and monoclonal gammopathy of undetermined significance. In patients with low finger-stick (capillary) glucose levels who do not display Whipple’s triad, and have comorbid conditions that might interfere with the BG reading, it is important for clinicians to recognize the difference between true and pseudohypoglycemia. This can be confirmed with a simultaneously done normal serum glucose level and will prevent unnecessary investigations or excessive treatment. Presentation: 6/3/2024

An Investigation of Cerebral Vascular Functional Properties in Middle-to-Old Age Community People With High Vascular Risk Profiles.

Vascular degeneration is an important cause of brain damage in aging. Assessing the functional properties of the cerebral vascular system may aid early diagnosis and prevention. To investigate the relationships between potential vascular functional markers and vascular risks, brain parenchymal damage, and cognition. Retrospective. Two hundred two general community subjects (42-80 years, males/females: 127/75). 3 T, spin echo T1W/T2W/FLAIR, resting-state functional MRI with an echo-planar sequence (rsfMRI), pseudo-continuous arterial spin labeling (pCASL) with a three-dimensional gradient-spin echo sequence. Cerebral blood flow (CBF) in gray matter calculated using pCASL, blood transit times calculated using rsfMRI, and the SD of internal carotid arteries signal (ICAstd) calculated using rsfMRI; visual assessment for lacunes; quantification of white matter hyperintensity volume; permutation test for quality control; collection of demographic and clinical data, Montreal Cognitive Assessment, Mini-Mental State Examination. Kolmogorov-Smirnov test; Spearman rank correlation analysis; Multivariable linear regression analysis controlling for covariates; The level of statistical significance was set at P < 0.05. Age was negatively associated with ICAstd (β = -0.180). Diabetes was associated with longer blood transit time from large arteries to capillary bed (β = 0.185, adjusted for age, sex, and intracranial volume). Larger ICAstd was associated with less presence of lacunes (odds ratio: 0.418, adjusted for age and sex). Higher gray matter CBF (β = 0.154) and larger ICAstd (β = 0.136) were associated with better MoCA scores (adjusted for age, sex, and education). Prolonged blood transit time, decreased ICAstd, and diminished CBF were associated with vascular dysfunction and cognitive impairment. They may serve as vascular functional markers in future studies. 3 TECHNICAL EFFICACY: Stage 3.

Using carpet plots to analyze blood transit times in the brain during hypercapnic challenge magnetic resonance imaging.

Blood arrival time and blood transit time are useful metrics in characterizing hemodynamic behaviors in the brain. Functional magnetic resonance imaging in combination with a hypercapnic challenge has been proposed as a non-invasive imaging tool to determine blood arrival time and replace dynamic susceptibility contrast (DSC) magnetic resonance imaging, a current gold-standard imaging tool with the downsides of invasiveness and limited repeatability. Using a hypercapnic challenge, blood arrival times can be computed by cross-correlating the administered CO2 signal with the fMRI signal, which increases during elevated CO2 due to vasodilation. However, whole-brain transit times derived from this method can be significantly longer than the known cerebral transit time for healthy subjects (nearing 20s vs. the expected 5-6s). To address this unrealistic measurement, we here propose a novel carpet plot-based method to compute improved blood transit times derived from hypercapnic blood oxygen level dependent fMRI, demonstrating that the method reduces estimated blood transit times to an average of 5.32s. We also investigate the use of hypercapnic fMRI with cross-correlation to compute the venous blood arrival times in healthy subjects and compare the computed delay maps with DSC-MRI time to peak maps using the structural similarity index measure (SSIM). The strongest delay differences between the two methods, indicated by low structural similarity index measure, were found in areas of deep white matter and the periventricular region. SSIM measures throughout the remainder of the brain reflected a similar arrival sequence derived from the two methods despite the exaggerated spread of voxel delays computed using CO2 fMRI.

Effect of Pemafibrate on Hemorheology in Patients with Hypertriglyceridemia and Aggravated Blood Fluidity Associated with Type 2 Diabetes or Metabolic Syndrome

Persistent high serum triglyceride (TG) and free fatty acid (FFA) levels, which are common in metabolic syndrome and type 2 diabetes, are risk factors for cardiovascular events because of exacerbated hemorheology. To explore the effects of pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, on hemorheology, we performed a single-center, nonrandomized, controlled study in patients with type 2 diabetes (HbA1c 6-10%) or metabolic syndrome, with fasting TG levels of ≥ 150 mg/dL and a whole blood transit time of > 45 s on a microarray channel flow analyzer (MCFAN). Patients were divided into a study group, receiving 0.2 mg/day of pemafibrate (n = 50) for 16 weeks, and a non-pemafibrate control group (n = 46). Blood samples were drawn 8 and 16 weeks after entry to the study to evaluate whole blood transit time as a hemorheological parameter, leukocyte activity by MCFAN, and serum FFA levels. No serious adverse events were observed in either of the groups. After 16 weeks, the pemafibrate group showed a 38.6% reduction in triglycerides and a 50.7% reduction in remnant lipoproteins. Pemafibrate treatment did not significantly improve whole blood rheology or leukocyte activity in patients with type 2 diabetes mellitus or metabolic syndrome complicated by hypertriglyceridemia and exacerbated hemorheology.

Red cell exchange transfusions increase cerebral capillary transit times and may alter oxygen extraction in sickle cell disease.

Persons with sickle cell disease (SCD) suffer from chronic hemolytic anemia, reduced blood oxygen content, and lifelong risk of silent and overt stroke. Major conventional stroke risk factors are absent in most individuals with SCD, yet nearly 50% have evidence of brain infarcts by the age of 30 years, indicating alternative etiologies for ischemia. We investigated whether radiological evidence of accelerated blood water transit through capillaries, visible on arterial spin labeling (ASL) magnetic resonance imaging, reduces following transfusion-induced increases in hemoglobin and relates to oxygen extraction fraction (OEF). Neurological evaluation along with anatomical and hemodynamic imaging with cerebral blood flow (CBF)-weighted pseudocontinuous ASL and OEF imaging with T2 -relaxation-under-spin-tagging were applied in sequence before and after blood transfusion therapy (n = 32) and in a comparator cohort of nontransfused SCD participants on hydroxyurea therapy scanned at two time points to assess stability without interim intervention (n = 13). OEF was calculated separately using models derived from human hemoglobin-F, hemoglobin-A, and hemoglobin-S. Gray matter CBF and dural sinus signal, indicative of rapid blood transit, were evaluated at each time point and compared with OEF using paired statistical tests (significance: two-sided p < 0.05). No significant change in sinus signal was observed in nontransfused participants (p = 0.650), but a reduction was observed in transfused participants (p = 0.034), consistent with slower red cell transit following transfusion. The dural sinus signal intensity was inversely associated with OEF pretransfusion (p = 0.011), but not posttransfusion. Study findings suggest that transfusion-induced increases in total hemoglobin may lengthen blood transit times through cerebral capillaries and alter cerebral OEF in SCD.

Capillary dysfunction correlates with cortical amyloid load in early Alzheimer's disease

Alterations in cerebral perfusion is increasingly considered to play a crucial role in Alzheimer's disease (AD) and together with accumulated amyloid-β, deficiencies in the brain microvascular circulation may result in local hypoxia. Here, we studied alterations in cerebral circulation and the correlation between amyloid-β load and cerebral perfusion in prodromal AD (pAD). Using dynamic susceptibility contrast MRI and PET, we evaluated cerebral perfusion and amyloid-β levels in 19 individuals with mild cognitive impairment (MCI) and high amyloid-β load (pAD-MCI), 13 MCI individuals without AD pathology and 21 healthy controls. The pAD-MCI group showed significantly lower microvascular blood flow and significantly higher heterogeneity of microvascular blood transit times (p < 0.01) compared with the other 2 groups. Additionally, in the pAD-MCI group raised amyloid-β levels correlated with decreased microvascular blood flow and increased heterogeneity of microvascular blood flow in frontal and temporal areas (p < 0.01). These results indicate a close connection between levels of amyloid-β deposition and brain microvascular perfusion in pAD. A vicious cycle may be established where amyloid-β load and deficiencies in brain perfusion may reinforce each other.

Comparing Velocity and Mean Arterial Pressure to Assess Pulsatility in Patients with Continuous Flow Left Ventricular Assist Devices

<h3>Purpose</h3> An increasing number of end-stage heart failure patients are supported by continuous-flow Left Ventricular Assist Devices (cfLVADs). In these patients, accurate assessment of arterial pulsatility remains a challenge because of diminished pulse pressure. Limited pulsatility in modern cfLVADs itself can be associated with adverse events such as stroke. Our study investigates the value of simultaneous arterial pressure and arterial blood velocity assessment in cfLVAD patients. <h3>Methods</h3> Both velocity (cm/s) and pressure (mmHg) data were collected during routine follow up. Pressure was measured using a brachial cuff oscillometry system (Sphygmocor XCel) providing a systolic and diastolic readings, while velocity was measured using a digital doppler (Huntleigh) from the brachial artery. Velocity measurements obtained included peak, minimum, average velocity and pulsatility index. Pressure measurements obtained were systolic and diastolic which allowed us to derive a mean arterial pressure (MAP) from the brachial artery. <h3>Results</h3> From a total of 24 patients (88% males), there were 44 velocity and pressure measurements. Mean device support duration was 240 days (SD 116). Mean derived brachial MAP was 85 mmHg (SD 9), whereas mean peak brachial artery velocity was 14 cm/s (SD 9). Mean pulsatility index was 2 (SD 2). Correlation analysis using Spearman's rho demonstrated a significant inverse relationship between Brachial derived MAP and Peak velocity (Rho=-0.41, p=0.007). <h3>Conclusion</h3> Arterial doppler measurements may provide incremental value over purely pressure-based measurements. The inverse relationship between derived MAP and peak velocity in this study may be partially explained by the degree of arterial compliance. In turn, this provides significant information on the relationship between higher MAP and lower blood velocity to subsequently explain increased thrombus formation and stroke rate due to longer transit time of blood.

Echocardiogram Unmasked Hemodynamic Advantage of Atrial Pacing in Securing Ventricular Preload in a Fontan Patient with Junctional Rhythm

While the advancement of perioperative management has expanded Fontan candidacy, not all patients have a successful postoperative course. Our case was a right isomerism patient who could not leave the ICU due to high central venous pressure and low output syndrome. Initial observation of the monitor ECG showed his rhythm to be supraventricular, however, an echocardiogram indicated simultaneous contraction of the atrium and ventricle, implying a junctional rhythm. While neither central venous pressure nor blood pressure improved with temporary pacing, better central venous and pulmonary venous blood flow patterns during pacing unraveled its positive impact. The patient successfully left the ICU after permanent pacing implantation. Hemodynamic study revealed a beneficial impact of atrial pacing in securing cardiac output and ventricular preload, lowering central venous pressure, and shortening blood transit time, which is partly attributed to the optimization of the fenestration function in reservation of the preload. Our case emphasizes the significant advantage of atrial pacing in a failing Fontan patient with junctional rhythm by reducing venous congestion and maximizing the benefit of fenestration.

Dynamic microcirculation PIPE model for functional neuroimaging, non-neuroimaging, and coherent hemodynamics spectroscopy: blood volume and flow velocity variations, and vascular autoregulation.

We present a dynamic microcirculation PIPE model for functional neuroimaging, non-neuroimaging, and coherent hemodynamics spectroscopy. The temporal evolution of the concentration and oxygen saturation of hemoglobin in tissue, comprised of the contributions from the arterioles, capillaries, and venules of microvasculature, is determined by time-resolved hemodynamic and metabolic variations in blood volume, flow velocity, and oxygen consumption with a fluid mechanics treatment. Key parameters regarding microcirculation can be assessed, including the effective blood transit times through the capillaries and the venules, and the rate constant of oxygen release from hemoglobin to tissue. The vascular autoregulation can further be quantified from the relationship between the resolved blood volume and flow velocity variations. The PIPE model shows excellent agreement with the experimental cerebral and cutaneous coherent hemodynamics spectroscopy (CHS) and fMRI-BOLD data. It further identifies the impaired cerebral autoregulation distinctively in hemodialysis patients compared to healthy subjects measured by CHS. This new dynamic microcirculation PIPE model provides a valuable tool for brain and other functional studies with hemodynamic-based techniques. It is instrumental in recovering physiological parameters from analyzing and interpreting the signals measured by hemodynamic-based neuroimaging and non-neuroimaging techniques such as functional near-infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI) in response to brain activation, physiological challenges, or physical maneuvers.

1106-P: Effects of Long-Term Dapagliflozin Treatment on Hemorheology (D-PATH Study)

Introduction: Hemorheology (blood viscosity) was reported to be a strong predictor of cardiovascular events in the Edinburgh Artery Study. However, deterioration in hemorheology through microvessels is a potential adverse effect of Sodium-glucose cotransporter-2 (SGLT2) inhibitors. This study aimed to clarify the effect of dapagliflozin on blood fluidity. Method: This multi-center, open-label, randomized, comparative study included 90 patients with type 2 diabetes mellitu. Patients were randomly divided into treatment groups with and without dapagliflozin treatment, and each item was investigated. The primary endpoint was the whole blood transit time, based on the difference from the baseline to 16 weeks after enrollment, as measured by a microchannel array flow analyzer (MC-FAN). To assess this outcome, a 15% noninferiority margin (clinically significant cut-off value) was used. To test the noninferiority of the treatment, a t-distribution was used to calculate the 95% confidence interval to assess the difference from the baseline. Results: The whole blood transit time in the dapagliflozin group was 41.8 ± 6.1 sec (mean ± SD) before administration, and 43.4 ± 6.8 sec at 16 weeks after dapagliflozin administration. In the control group, the whole blood transit time was 40.5 ± 3.0 sec before administration and 39.9 ± 3.8 sec after 16 weeks. The difference between groups from the baseline to 16 weeks after enrollment was 1.7 sec [0.2, 3.5] (95% C.I), confirming the noninferiority of dapagliflozin administration. Futher, the analysis Results of the differences between groups according to the some items (the baseline of hematocrit, HbA1c levels and the whole blood transit time) for baseline, demonstrating the noninferiority of dapagliflozin administration in these items. Conclusion: Dapagliflozin was unlikely to have negative effects on blood fluidity after administration irrespective of the baseline Hematocrit, HbA1c levels and the whole blood transit time. Disclosure S. Ono: None. Y. Nakatani: None. A. Kawabe: None. Y. Miyashita: None. M. Matsumura: None. N. Banba: None. Y. Aso: None. T. Yasu: None. Funding AstraZeneca

Quantitative Angiographic Hemodynamic Evaluation After Revascularization Surgery for Moyamoya Disease

The corresponding hemodynamic changes of the internal carotid artery (ICA) after the revascularization surgery for moyamoya disease (MMD) remain unclear. The aim of this study was to analyze the hemodynamic changes of the ipsilateral ICA after the combined direct and indirect extracranial-intracranial (EC-IC) bypass. MMD patients undergoing combined EC-IC bypass were retrospectively reviewed. The mean transit time (MTT) of ICA was evaluated by color-coding angiography before revascularization and at follow-up. The MTT defined as the blood transit time between the end of cervical portion (C1) and the C7 segment of ICA. The clinical prognosis was assessed with Matsushima grading system, moyamoya vessel reduction system, and modified Rankin Scale (mRS). The correlation between hemodynamic parameter and prognosis was analyzed. Subgroup analysis was conducted between different presentations and different ages. Fifty-one patients were identified and the mean imaging follow-up interval was 5.5 months. The ICA-MTT was increased after the combined revascularization (P < 0.001) compared with contralateral ICA. Faster preoperative ICA-MTT was significantly associated with improved mRS in the ischemic group (P = 0.05). The increased ICA-MTT was significantly associated with favorable neoangiogenesis (P = 0.04), moyamoya vessel reduction (> 50%) (P = 0.023), and improved mRS score (P = 0.008). In subgroup analysis, the correlation in the ischemic subgroup and adult subgroup remained significant. In this cohort, the ICA-MTT increased after the combined EC-IC bypass, and there was a positive correlation between the increased blood transit time and favorable outcomes. Color-coding DSA proved to be useful as a quantitative and serial method to monitor postoperative courses after revascularization in MMD.

Relative Cerebral Blood Transit Time Decline and Neurological Improvement in Patients After Internal Carotid Artery Stenting.

In this study we hypothesized that the alleviation of neurological symptoms long after internal carotid artery (ICA) stenting may be related to sustained improvement of cerebral perfusion. Thirty-four subjects (F/M; 15/19) with >70% stenosis of a single internal carotid artery and neurological symptoms, who underwent a carotid artery stenting procedure, were studied. Brain computed tomography perfusion (CTP) imaging was performed before and 3years after ICA stenting. The following relative variables were compared: cerebral blood flow (rCBF), cerebral blood volume (rCBV), mean transit time (rMTT), time to peak (rTTP), and permeability surface area product (rPS). A survey also was conducted to compare the patients' clinical symptoms. Overall, we found that a trend toward rMTT decline was the only persisting change after ICA stenting. We then stratified the patients into the subgroups of <2%, 2-5%, and>5% rMTT decline and found that those with a rMTT decline >2% reported a prominent reduction in subjective clinical symptoms such as headache, dizziness, tinnitus, blurred vision, transient blindness, a sense of gravity of the head, and pain in the eyeballs. We conclude that a shortened mean rMTT, likely reflecting improved cerebral microcirculation, underlies the improvement of neurological symptoms in patients with ICA stenosis.

Left ventricular diastolic dysfunction and exertional ventilatory inefficiency in COPD.

Left ventricular diastolic dysfunction (LVDD) is highly prevalent in COPD and conflicting results have emerged regarding the consequences on exercise capacity in the 6MWT. We sought to examine the ventilatory efficiency and variability metrics as the primary endpoint and aerobic capacity (V'O2) as the secondary endpoint. Forty subjects were included and submitted to comprehensive lung function tests, detailed pulsed-Doppler echocardiography, and cardiopulmonary exercise testing. Four subjects were excluded due to concomitant cardiac disease and two owing to COPD exacerbation. Seventeen COPD/LVDD+ and seventeen COPD/LVDD-individuals were closely matched for baseline characteristics. Throughout the exercise, there was no difference between-groups for primary (V'E/V'CO2slope and V'E/V'CO2nadir, p > 0.05 for both) or secondary endpoints (V'O2peak%pred, p>0.05). Ventilatory variability remained unchanged. However, after very well age- and sex-matched subgroup analysis, five-moderate and three-mild COPD/LVDD+subjects with elevated left ventricular filling pressure (E/e'>13, n=8), presented a downward-shifted V'E/V'CO2slope (25.7 ± 5.1 vs 33.4 ± 7.1, p = 0.031) and V'E/V'CO2nadir reduction (29.7 ± 3.9 vs 36.3 ± 7.2, p = 0.042) besides significantly better V'O2peak%pred (92.1 ± 21.6% vs 75.8 ± 13.1%, p = 0.045) compared to 8 COPD/LVDD-controls. Ventilatory variability remained once again unchanged. COPD/LVDD overlap is not associated with worse exercise tolerance and/or wasted ventilation in excess compared to controls, even when suspected for elevated left ventricular filling pressure. Further studies are warranted to study specifically if augmented pulmonary blood transit time can allow better gas-exchange, thus preserving exercise capacity under specific conditions in COPD patients without heart failure.

Spatial-temporal perfusion patterns of the human liver assessed by pseudo-continuous arterial spin labeling MRI

PurposeTo investigate the capabilities of a modern pseudo-continuous arterial spin labeling (PCASL) technique for non-invasive assessment of the temporal and spatial distribution of the liver perfusion in healthy volunteers on a clinical MR system at 3T. Materials and methodsA 2D-PCASL multi-slice echo planar imaging sequence was adapted to the specific conditions in liver: a) labeling by PCASL was optimized to the flow characteristics in the portal vein, b) background suppression was applied for reduction of motion related artifacts, c) post labeling delays (PLDs) were varied over a large range (0.7–3.5s) in order to get better insight in the temporal and spatial distribution of tagged blood in the liver, and d) a special timed-breathing protocol was used allowing for recording of 16 to 18 label-control image pairs and a reference M0 image for each of 4 to 6 slices within approx. 5min for one PLD. ResultsMeasurements with multiple PLDs showed dominating perfusion signal in macroscopic blood vessels for PLDs up to 1.5 s, whereas pure liver parenchyma revealed maximum perfusion signal for a PLD of approx. 2 s, and detectable signal up to PLDs of 3.5 s. Data fitting to a perfusion model for liver provided a mean global perfusion of 153±15ml/100g/min and a mean transit time of 1938±332ms in liver parenchyma. Measurements with a single PLD of 2 s demonstrated that portal-venous and arterial perfusion components can be measured separately by two measurements with two different positions of the labeling plane (one for labeling of the global hepatopetal blood flow and one for selective labeling of the portal blood flow only). Relative contribution of blood from the hepatic artery to the global liver perfusion, the hepatic perfusion index (HPI), amounted to approx. 23%. ConclusionModern and adapted protocols for assessment of liver perfusion by PCASL have the potential to provide perfusion and blood transit time maps in reasonable acquisition time.

Contribution of systemic vascular effects to fMRI activity in white matter

To investigate a potential contribution of systemic physiology to recently reported BOLD fMRI signals in white matter, we compared photo-plethysmography (PPG) and whole-brain fMRI signals recorded simultaneously during long resting-state scans from an overnight sleep study. We found that intermittent drops in the amplitude of the PPG signal exhibited strong and widespread correlations with the fMRI signal, both in white matter (WM) and in gray matter (GM). The WM signal pattern resembled that seen in previous resting-state fMRI studies and closely tracked the location of medullary veins. Its temporal cross-correlation with the PPG amplitude was bipolar, with an early negative value. In GM, the correlation was consistently positive. Consistent with previous studies comparing physiological signals with fMRI, these findings point to a systemic vascular contribution to WM fMRI signals. The PPG drops are interpreted as systemic vasoconstrictive events, possibly related to intermittent increases in sympathetic tone related to fluctuations in arousal state. The counter-intuitive polarity of the WM signal is explained by long blood transit times in the medullary vasculature of WM, which cause blood oxygenation loss and a substantial timing mismatch between blood volume and blood oxygenation effects. A similar mechanism may explain previous findings of negative WM signals around large draining veins during both task- and resting-state fMRI.

Pulmonary transit time derived from pulmonary angiography for the diagnosis of hepatopulmonary syndrome.

Pulmonary transit time (PTT) is the transit time of blood from the right side of the heart to the left side of the heart. The aim of the present study was to evaluate the role of the PTT derived from pulmonary angiography in the diagnosis of hepatopulmonary syndrome (HPS). From December 2014 to September 2015, all patients with chronic liver disease and/or portal hypertension undergoing a venous interventional radiologic procedure at our institution were eligible for inclusion in this prospective study. Pulmonary angiography was performed in all patients, and the PTT, which was defined as the time between opacification of the pulmonary trunk and the right border of the left atrium, was determined. A total of 53 patients were included, 20 of whom had a positive contrast-enhanced echocardiography result and an elevated alveolar-arterial oxygen gradient were considered to have HPS. PTT was significantly shorter in patients with HPS than in those without [median, 3.34 (interquartile range, 3.01-3.67)seconds vs 4.0 (interquartile range, 3.67-4.17)seconds; P<.001]. The area under the receiver operating characteristic curve of PTT for diagnosing HPS was 0.83 (95% confidence interval, 0.70-0.92). The optimal cut-off value of PTT for diagnosing HPS, based on Youden's index, was 3.55seconds. The sensitivity, specificity and accuracy of PTT<3.55seconds for diagnosing HPS were 70%, 85% and 79% respectively. Pulmonary transit time derived from pulmonary angiography is useful for diagnosing HPS, especially for patients with intracardiac shunts and inadequate echocardiographic windows.

The resting-state fMRI arterial signal predicts differential blood transit time through the brain

Previous studies have found that aperiodic, systemic low-frequency oscillations (sLFOs) are present in blood-oxygen-level-dependent (BOLD) data. These signals are in the same low frequency band as the “resting state” signal; however, they are distinct signals which represent non-neuronal, physiological oscillations. The same sLFOs are found in the periphery (i.e. finger tips) as changes in oxy/deoxy-hemoglobin concentration using concurrent near-infrared spectroscopy. Together, this evidence points toward an extra-cerebral origin of these sLFOs. If this is the case, it is expected that these sLFO signals would be found in the carotid arteries with time delays that precede the signals found in the brain. To test this hypothesis, we employed the publicly available MyConnectome dataset (a two-year longitudinal study of a single subject) to extract the sLFOs in the internal carotid arteries (ICAs) with the help of the T1/T2-weighted images. Significant, but negative, correlations were found between the LFO BOLD signals from the ICAs and (1) the global signal (GS), (2) the superior sagittal sinus, and (3) the jugulars. We found the consistent time delays between the sLFO signals from ICAs, GS and veins which coincide with the blood transit time through the cerebral vascular tree.

Perfusion criteria of the EICMA efficacy in patients with symptomatic occlusion of the internal carotid artery

To investigate changes in cerebral perfusion in patients with unilateral internal carotid artery occlusion before and after surgical revascularization of the brain, depending on the clinical efficacy of surgical treatment. The study included 60 patients with unilateral ICA occlusions who underwent placement of an extra-intracranial microvascular anastomosis (EICMA). All patients underwent a CT perfusion study before and after cerebral revascularization. In addition, the degree of neurological deficit was evaluated before surgery and during follow-up (3 and 8-10 months) using the NIHSS score. All patients were divided into 3 groups, depending on the results of surgical treatment: objective improvement (43 patients), no changes (14 patients), and worsening of clinical symptoms (3 patients). In each group, the absolute and relative perfusion parameters (MTT, CBV, and CBF) were analyzed to identify the perfusion criteria for the EICMA efficacy. A significant relationship between the clinical efficacy of EICMA and a baseline perfusion deficit and its change after anastomosis placement was found. Placement of EICMA is effective treatment for patients with symptomatic ICA occlusions and an increase in the blood transit time in the hemisphere ipsilateral to occlusion by more than 40% compared to that in the opposite side provided that perfusion is recovered in more than one area of the MCA territory (in accordance with the ASPECTS scale).

Abstract B24: Impact of aerobic exercise on tumor oxygenation and perfusion in breast cancer

Abstract The purpose of this study is to evaluate the effects of low to moderate aerobic exercise on tumor vasculature, perfusion and oxygenation in breast cancer. Poor perfusion and hypoxia are common features of solid tumors that are a result of abnormal tumor angiogenesis. Both chemo- and radiation therapies are negatively affected by tumor hypoxia, with the presence of hypoxia associated with treatment failure and poor outcomes in cancer patients. While strategies to enhance tumor oxygenation and perfusion have been developed, their success in the clinic has been limited. A potential method to increase oxygenation and decrease hypoxia that is safe and well-tolerated is aerobic exercise. The benefits of exercise as a palliative measure are well documented, however the effects of exercise on tumor blood flow and oxygenation have not been extensively characterized. Histological analysis of vessel density (MECA-32), vessel perfusion (Hoechst-33342) and hypoxia (EF5) were quantified in tumor bearing mice subjected to low to moderate intensity treadmill running and compared to sedentary control mice. In a separate model, a murine dorsal skinfold window chamber model and in vivo microscopy of microvessel function was utilized to characterize changes in tumor vascular structure and function in real time. In these studies, the combination of hyperspectral imaging of hemoglobin (Hb) saturation and first-pass fluorescence (FPF) imaging of blood transit time were used. Hb saturation imaging reveals the oxygenation of blood within microvessels while FPF imaging gives information regarding blood flow and network connections by recording a fluorescent contrast agent as it is injected into circulation. Spectroscopic analysis was performed in female nude mice with surgically installed titanium window chambers. Mammary tumors were initiated in the windows and once tumors reached a specified volume, animals were subjected to daily treadmill running for up to a week. As a sedentary control, mice were placed on a stationary treadmill for equivalent periods of time. Combination imaging was performed daily to monitor microvessel oxygenation and blood flow. Preliminary results indicate that following one bout of exercise, tumor perfusion is increased, however there was no significant correlation between exercise and tumor microvessel oxygenation. For histological analysis, mammary tumors were initiated in the fat pad of female nude mice. Once tumors nodules were established, animals were subjected to either a single bout or daily bouts of exercise for 1 to 5 weeks. Sedentary controls were exposed to a stationary treadmill for equivalent periods of time. Following exercise protocols, tumors were harvested and sectioned for immunohistochemical analysis. Staining analysis revealed an improvement in tumor oxygenation and an increase in the number of perfused vessels in tumors of exercising animals in comparison to sedentary controls. Our results demonstrate aerobic exercise can increase tumor oxygenation and perfusion in breast cancer, suggesting that exercise can potentially be used as an adjunctive therapy to overcome tumor hypoxia and enhance the efficacy of chemo- and radiation therapy. Citation Format: Jennifer A. Lee, Jennifer Wiggins, Dietmar W. Siemann. Impact of aerobic exercise on tumor oxygenation and perfusion in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B24.

Beta blockade increases pulmonary and systemic transit time heterogeneity: evaluation based on indocyanine green kinetics in healthy volunteers.

Knowledge of factors influencing the heterogeneity of blood transit times is important in cardiovascular physiology. The aim of the study was to investigate the effect of beta-adrenergic blockade on blood transit time dispersion in awake, anxious volunteers. Recirculatory modelling of the disposition of intravascular markers using parametric forms for transit time distributions, such as the inverse Gaussian distribution, provides the opportunity to estimate the systemic and pulmonary transit time dispersion invivo. The latter is determined by the flow heterogeneity in the microcirculatory network. Using this approach, we have analysed indocyanine green (ICG) disposition data obtained in four subjects by frequent early arterial blood sampling before and after beta-adrenergic blockade by propranolol. Propranolol decreased cardiac output from 9·3±2·8lmin-1 to 3·5±0·47lmin-1 (P<0·05). This reduction was accompanied by a 4·5±0·6-fold and 2·1±0·3-fold increase (P<0·001) in the relative dispersion (dimensionless variance) of blood transit times through the systemic and pulmonary circulation, respectively.