Pulmonary blood volume measured by 82Rb-PET in patients with chronic obstructive pulmonary disease: a retrospective cohort study.

In patients with chronic obstructive pulmonary disease (COPD), pulmonary vascular dysfunction and destruction are observable before the onset of detectable emphysema, but it is unknown whether this is associated with central hypovolemia. We investigated if patients with COPD have reduced pulmonary blood volume (PBV) evaluated by 82Rb-positron emission tomography (PET) at rest and during adenosine-induced hyperemia. This single-center retrospective cohort study assessed 6,301 82Rb-PET myocardial perfusion imaging (MPI) examinations performed over a 6-yr period. We compared 77 patients with COPD with 44 healthy kidney donors (controls). Cardiac output ([Formula: see text]) and mean 82Rb bolus transit time (MBTT) were used to calculate PBV. [Formula: see text] was similar at rest (COPD: 3,649 ± 120 mL vs. control: 3,891 ± 160 mL, P = 0.368) but lower in patients with COPD compared with controls during adenosine infusion (COPD: 5,432 ± 124 mL vs. control: 6,185 ± 161 mL, P < 0.050). MBTT was shorter in patients with COPD compared with controls at rest (COPD: 8.7 ± 0.28 s vs. control: 11.4 ± 0.37 s, P < 0.001) and during adenosine infusion (COPD: 9.2 ± 0.28 s vs. control: 10.2 ± 0.37 s, P < 0.014). PBV was lower in patients with COPD, even after adjustment for body surface area, sex, and age at rest [COPD: 530 (29) mL vs. 708 (38) mL, P < 0.001] and during adenosine infusion [COPD: 826 (29) mL vs. 1,044 (38) mL, P < 0.001]. In conclusion, patients with COPD show evidence of central hypovolemia, but it remains to be determined whether this has any diagnostic or prognostic impact.NEW & NOTEWORTHY The present study demonstrated that patients with chronic obstructive pulmonary disease (COPD) exhibit central hypovolemia compared with healthy controls. Pulmonary blood volume may thus be a relevant physiological and/or clinical outcome measure in future COPD studies.

Prognostic implications of volume status assessed by blood volume analysis in ambulatory heart failure.

The prognostic implications of intravascular volume status assessed by blood volume analysis (BVA) in ambulatory heart failure (HF) remain uncertain. The incremental benefits of assessing volume status, beyond the well-established filling pressures, in predicting HF outcomes are unknown.

Comparison of intradialytic continuous and interval training on hemodynamics and dialysis adequacy: A crossover randomized controlled trial.

AIM: Circulating blood volume (BV) during exercise changes depending on the intensity and duration, and post-exercise hypotension is observed after continuous exercise. We investigated the safety and efficacy of both interval and continuous IDE at anaerobic threshold (AT) levels with respect to hemodynamic stability and dialysis efficiency. METHODS: In this crossover randomized controlled trial, 16 patients on haemodialysis were subjected to three trial arms, including non-IDE, interval-IDE, and continuous-IDE arms. Systolic blood pressure (SBP), BV, and ultraviolet absorbance - an indicator of dialysis efficiency - were continuously measured, and each change was compared between the three arms by two-way analysis of variance. RESULTS: Continuous IDE decreased SBP from post-exercise to the end of dialysis compared with baseline (pre 142.8 ± 19.0 vs. post 127.5 ± 24.5 mmHg, p = .02), whereas interval IDE maintained better SBP levels post-exercise (pre 139.9 ± 17.1 vs. post 140.1 ± 15.8 mmHg, p = 1.0) than continuous IDE (non-IDE 133.2 ± 19.9 vs. interval 140.1 ± 15.8 vs. continuous 127.5 ± 24.5 mmHg, p = .04). Moreover, interval IDE caused less tiredness and few symptoms (p < .05), despite reaching higher intensity than continuous IDE (p = .001). The BV of each IDE arm decreased during exercise and recovered post-exercise to the same level as non-IDE. Ultraviolet absorbance was not different between each arm (p = .16). CONCLUSION: AT-level interval IDE maintains better hemodynamic stability from post-exercise to the end of dialysis and may represent a novel approach that can be effectively performed with fewer symptoms.

Study of the f-cell ratio using plasma dilution and albumin mass kinetics.

BACKGROUND: The f-cell ratio of 0.91 is a conversion factor between the hematocrit measured in peripheral blood and the hematocrit obtained by separate measurements of the red blood cell mass and plasma volume. The physiological background of the f-cell ratio is unclear. METHODS: Data were retrieved from 155 intravenous infusion experiments where 15-25 mL/kg of crystalloid fluid diluted the blood hemoglobin and plasma albumin concentrations. The hemodilution was converted to plasma dilution using the peripheral hematocrit, and the volume of distribution of exogenous albumin was calculated in 41 volunteers who received 20 % or 5 % albumin by intravenous infusion. Finally, the kinetics of plasma albumin was studied during 98 infusion experiments with 20 % albumin. RESULTS: Plasma dilution based on hemoglobin and albumin showed a median difference of -0.001 and a mean difference of 0.000 (N = 2184), which demonstrates that these biomarkers indicate the same expandable vascular space. In contrast, exogenous albumin occupied a volume that was 10 % larger than the plasma volume indicated by the anthropometric equations of Nadler et al. and Retzlaff et al. The kinetic analysis identified a secondary compartment that was 450 mL in size and rapidly exchanged albumin with the circulating plasma. CONCLUSIONS: The results suggest that the f-cell ratio is due to rapid exchange of albumin between the plasma and a non-expandable compartment located outside the circulating blood (possibly the liver sinusoids). This means that the hematocrit measured in peripheral blood correctly represents the ratio between the red cell volume and the circulating plasma volume.

Vascular refilling depends on the ratio of blood volume to extracellular volume in hemodialysis patients.

The ratio of blood volume to extracellular volume is approximately one to three under physiological conditions and also in stable chronic hemodialysis patients. Recently, it was found that this ratio remains unchanged during hemodialysis despite ultrafiltration. This would signify that the higher the ratio, the lower the refilling and vice versa. To test this hypothesis, treatment data of a previous study were re-analyzed. In 79 stable chronic hemodialysis patients, the refilling fraction was 0.749 ± 0.094. There was a significant negative correlation (r = -0.412; p < 0.001) between the blood volume to extracellular volume ratio and the refilling fraction. The blood volume to extracellular volume relationship seems to be a significant determinant of vascular refilling: the higher the ratio, the lower the refilling, and vice versa.

Selective elevation in external carotid artery flow during acute gravitational transition to microgravity during parabolic flight.

This study sought to determine to what extent acute exposure to microgravity (0 G) and related increases in central blood volume (CBV) during parabolic flight influence the regional redistribution of intra and extra cranial cerebral blood flow (CBF). Eleven healthy participants performed during two parabolic flights campaigns aboard the Airbus A310-ZERO G aircraft. The response of select variables for each of the 15 parabolas involving exposure to both 0 G and hypergravity (1.8 G) were assessed in the seated position. Mean arterial blood pressure (MAP) and heart rate (HR) were continuously monitored and used to calculate stroke volume (SV), cardiac output ([Formula: see text]), and systemic vascular resistance (SVR). Changes in CBV were measured using an impedance monitor. Extracranial flow through the internal carotid, external carotid, and vertebral artery ([Formula: see text]ICA, [Formula: see text]ECA, and [Formula: see text]VA), and intracranial blood velocity was measured by duplex ultrasound. When compared with 1-G baseline condition, 0 G increased CBV (+375 ± 98 mL, P = 0.004) and [Formula: see text] (+16 ± 14%, P = 0.024) and decreased SVR (-7.3 ± 5 mmHg·min·L-1, P = 0.002) and MAP (-13 ± 4 mmHg, P = 0.001). [Formula: see text]ECA increased by 43 ± 46% in 0 G (P = 0.030), whereas no change was observed for CBF, [Formula: see text]ICA, or [Formula: see text]VA (P = 0.102, P = 0.637, and P = 0.095, respectively).NEW & NOTEWORTHY Our findings demonstrate that in microgravity there is a selective increase in external carotid artery blood flow whereas global and regional cerebral blood flow remained preserved. To what extent this reflects an adaptive, neuroprotective response to counter overperfusion remains to be established.

Layer-fMRI VASO with short stimuli and event-related designs at 7 T.

Layers and columns are the dominant processing units in the human (neo)cortex at the mesoscopic scale. While the blood oxygenation dependent (BOLD) signal has a high detection sensitivity, it is biased towards unwanted signals from large draining veins at the cortical surface. The additional fMRI contrast of vascular space occupancy (VASO) has the potential to augment the neuroscientific interpretability of layer-fMRI results by means of capturing complementary information of locally specific changes in cerebral blood volume (CBV). Specifically, VASO is not subject to unwanted sensitivity amplifications of large draining veins. Because of constrained sampling efficiency, it has been mainly applied in combination with efficient block task designs and long trial durations. However, to study cognitive processes in neuroscientific contexts, or probe vascular reactivity, short stimulation periods are often necessary. Here, we developed a VASO acquisition procedure with a short acquisition period and sub-millimeter resolution. During visual event-related stimulation, we show reliable responses in visual cortices within a reasonable number of trials (∼20). Furthermore, the short TR and high spatial specificity of our VASO implementation enabled us to show differences in laminar reactivity and onset times. Finally, we explore the generalizability to a different stimulus modality (somatosensation). With this, we showed that CBV-sensitive VASO provides the means to capture layer-specific haemodynamic responses with high spatio-temporal resolution and is able to be used with event-related paradigms.

Serial blood volume measurements in patients with compensated chronic heart failure: How do volume profiles change over time?

Among patients with chronic heart failure (HF) intravascular volume profiles vary significantly despite similar clinical compensation. However, little is known regarding changes in blood volume (BV) profiles over time. The objective of this analysis was to identify the extent and character of changes in volume profiles over time. A prospective analysis was undertaken in patients who were hospitalized and treated for fluid overload. Quantitative BV analyses were obtained in a compensated state at hospital discharge (baseline) and follow-up at 1, 3, and 6 mo. Data were available on 10 patients who remained stable without rehospitalization or medication change over a 6-mo period. Baseline BV profiles were highly variable at hospital discharge with an average deviation of +28% above normal in 6 patients and normal BV in 4 patients. Over the follow-up period, the median change in BV was -201 mL [-3% (-6, +3%)] from baseline with profiles remaining in the same volume category in 9 out of 10 patients. Crossover from normal BV to mild contraction (-13% of normal) occurred in one patient. Red blood cell mass demonstrated the largest change over 6 mo [median -275 (-410, +175) mL] with a deviation from normal of -14 (-20, +8) % (reflecting mild anemia). These findings suggest that BV profiles in clinically compensated patients with HF do not change substantially over a 6-mo period regardless of baseline expanded or normal BV. This lack of change in volume profiles particularly from an expanded BV has implications for long-term volume management, clinical outcomes, and also our understanding of volume homeostasis in HF.NEW & NOTEWORTHY The novel findings of this study demonstrate that blood volume profiles while highly variable in clinically compensated patients with HF on stable medical therapy do not change substantially over a 6-mo period regardless of baseline expanded or normal blood volumes. This lack of change in volume profiles particularly from an expanded blood volume has implications for long-term volume management and also for how we understand the pathophysiology of volume homeostasis in chronic HF.

Superiority of compensatory reserve measurement compared with the Shock index for early and accurate detection of reduced central blood volume status.

BACKGROUND: Shock index (SI) equals the ratio of heart rate (HR) to systolic blood pressure (SBP) with clinical evidence that it is more sensitive for trauma patient status assessment and prediction of outcome compared with either HR or SBP alone. We used lower body negative pressure (LBNP) as a human model of central hypovolemia and compensatory reserve measurement (CRM) validated for accurate tracking of reduced central blood volume to test the hypotheses that SI: (1) presents a late signal of central blood volume status; (2) displays poor sensitivity and specificity for predicting the onset of hemodynamic decompensation; and (3) cannot identify individuals at greatest risk for the onset of circulatory shock. METHODS: We measured HR, SBP, and CRM in 172 human subjects (19-55 years) during progressive LBNP designed to determine tolerance to central hypovolemia as a model of hemorrhage. Subjects were subsequently divided into those with high tolerance (HT) (n = 118) and low tolerance (LT) (n = 54) based on completion of 60 mm Hg LBNP. The time course relationship between SI and CRM was determined and receiver operating characteristic (ROC) area under the curve (AUC) was calculated for sensitivity and specificity of CRM and SI to predict hemodynamic decompensation using clinically defined thresholds of 40% for CRM and 0.9 for SI. RESULTS: The time and level of LBNP required to reach a SI = 0.9 (~60 mm Hg LBNP) was significantly greater ( p < 0.001) compared with CRM that reached 40% at ~40 mm Hg LBNP. Shock index did not differ between HT and LT subjects at 45 mm Hg LBNP levels. ROC AUC for CRM was 0.95 (95% CI = 0.94-0.97) compared with 0.91 (0.89-0.94) for SI ( p = 0.0002). CONCLUSION: Despite high sensitivity and specificity, SI delays time to detect reductions in central blood volume with failure to distinguish individuals with varying tolerances to central hypovolemia. LEVEL OF EVIDENCE: Diagnostic Test or Criteria; Level III.

The increase in cardiac output induced by a decrease in positive end-expiratory pressure reliably detects volume responsiveness: the PEEP-test study.

BACKGROUND: In patients on mechanical ventilation, positive end-expiratory pressure (PEEP) can decrease cardiac output through a decrease in cardiac preload and/or an increase in right ventricular afterload. Increase in central blood volume by fluid administration or passive leg raising (PLR) may reverse these phenomena through an increase in cardiac preload and/or a reopening of closed lung microvessels. We hypothesized that a transient decrease in PEEP (PEEP-test) may be used as a test to detect volume responsiveness. METHODS: Mechanically ventilated patients with PEEP ≥ 10 cmH2O ("high level") and without spontaneous breathing were prospectively included. Volume responsiveness was assessed by a positive PLR-test, defined as an increase in pulse-contour-derived cardiac index (CI) during PLR ≥ 10%. The PEEP-test consisted in reducing PEEP from the high level to 5 cmH2O for one minute. Pulse-contour-derived CI (PiCCO2) was monitored during PLR and the PEEP-test. RESULTS: We enrolled 64 patients among whom 31 were volume responsive. The median increase in CI during PLR was 14% (11-16%). The median PEEP at baseline was 12 (10-15) cmH2O and the PEEP-test resulted in a median decrease in PEEP of 7 (5-10) cmH2O, without difference between volume responsive and unresponsive patients. Among volume responsive patients, the PEEP-test induced a significant increase in CI of 16% (12-20%) (from 2.4 ± 0.7 to 2.9 ± 0.9 L/min/m2, p < 0.0001) in comparison with volume unresponsive patients. In volume unresponsive patients, PLR and the PEEP-test increased CI by 2% (1-5%) and 6% (3-8%), respectively. Volume responsiveness was predicted by an increase in CI > 8.6% during the PEEP-test with a sensitivity of 96.8% (95% confidence interval (95%CI): 83.3-99.9%) and a specificity of 84.9% (95%CI 68.1-94.9%). The area under the receiver operating characteristic curve of the PEEP-test for detecting volume responsiveness was 0.94 (95%CI 0.85-0.98) (p < 0.0001 vs. 0.5). Spearman's correlation coefficient between the changes in CI induced by PLR and the PEEP-test was 0.76 (95%CI 0.63-0.85, p < 0.0001). CONCLUSIONS: A CI increase > 8.6% during a PEEP-test, which consists in reducing PEEP to 5 cmH2O, reliably detects volume responsiveness in mechanically ventilated patients with a PEEP ≥ 10 cmH2O. Trial registration ClinicalTrial.gov (NCT 04,023,786). Registered July 18, 2019. Ethics Committee approval CPP Est III (N° 2018-A01599-46).

Dynamic contrast-enhanced computed tomography in 11 dogs with orofacial tumors.

OBJECTIVE: Treatment of orofacial tumors in dogs is associated with high morbidity and reliable prognostic factors are lacking. Dynamic contrast-enhanced computed tomography (DCECT) can be used to assess tumor perfusion. The objectives of this study were to describe the perfusion parameters of different types of orofacial tumors and to describe the changes in perfusion parameters during radiotherapy (RT) in a subset of them. ANIMALS: 11 dogs with orofacial tumors prospectively recruited. CLINICAL PRESENTATION AND PROCEDURES: All dogs had baseline DCECT to assess blood volume (BV), blood flow (BF), and transit time (TT). Five dogs had repeat DCECT during megavoltage RT. RESULTS: 5 squamous cell carcinomas, 3 sarcomas, 1 melanoma, 1 histiocytic sarcoma, and 1 acanthomatous ameloblastoma were included. Blood volume and BF were higher in squamous cell carcinomas than in sarcomas, although no statistical analysis was performed. At repeat DCECT, 4 dogs showed a reduction in the size of their tumor during RT. Among these dogs, 3 showed an increase in BV and BF and 1 a decrease in these parameters between the baseline and the follow-up DCECT. The only dog whose tumor increased in size between the first and the second DCECT showed a decrease in BV and BF. CLINICAL RELEVANCE: Perfusion parameters derived from DCECT were described in a series of dogs with various types of orofacial tumors. The results suggest that epithelial tumors could have higher BV and BF than mesenchymal tumors, although larger sample sizes are needed to support these preliminary findings.

Improved Selectivity in 7 T Digit Mapping Using VASO-CBV.

Functional magnetic resonance imaging (fMRI) at Ultra-high field (UHF, ≥ 7 T) benefits from significant gains in the BOLD contrast-to-noise ratio (CNR) and temporal signal-to-noise ratio (tSNR) compared to conventional field strengths (3 T). Although these improvements enabled researchers to study the human brain to unprecedented spatial resolution, the blood pooling effect reduces the spatial specificity of the widely-used gradient-echo BOLD acquisitions. In this context, vascular space occupancy (VASO-CBV) imaging may be advantageous since it is proposed to have a higher spatial specificity than BOLD. We hypothesized that the assumed higher specificity of VASO-CBV imaging would translate to reduced overlap in fine-scale digit representation maps compared to BOLD-based digit maps. We used sub-millimeter resolution VASO fMRI at 7 T to map VASO-CBV and BOLD responses simultaneously in the motor and somatosensory cortices during individual finger movement tasks. We assessed the cortical overlap in different ways, first by calculating similarity coefficient metrics (DICE and Jaccard) and second by calculating selectivity measures. In addition, we demonstrate a consistent topographical organization of the targeted digit representations (thumb-index-little finger) in the motor areas. We show that the VASO-CBV responses yielded less overlap between the digit clusters than BOLD, and other selectivity measures were higher for VASO-CBV too. In summary, these results were consistent across metrics and participants, confirming the higher spatial specificity of VASO-CBV compared to BOLD.

Longitudinal haematological responses to training load and heat acclimation preceding a male team pursuit cycling world record.

This study evaluated relationships between changes in training load, haematological responses, and endurance exercise performance during temperate and heat acclimation (HA) training preceding a male team cycling pursuit world record (WR). Haemoglobin mass (Hbmass) and concentration ([Hb]), plasma volume (PV) and blood volume (BV) were assessed in nine male track endurance cyclists (∼3 occasions per month) training in temperate conditions (247-142 days prior to the WR) to establish responses to differing acute (ATL) and chronic (CTL) training loads. Testing was performed again pre- and post-HA (22-28 days prior to the WR). Endurance performance (V̇O2max, 4MMP, lactate threshold 1 and 2) was assessed on three occasions (238-231, 189-182 and 133-126 days prior to the WR). In temperate conditions, CTL was associated with Hbmass (B = 0.62, P = 0.02), PV (B = 4.49, P = 0.01) and BV (B = 6.51, P = 0.04) but not [Hb] (B = -0.01, P = 0.17). ATL was associated with PV (B = 2.28, P < 0.01), BV (B = 2.63, P = 0.04) and [Hb] (B = -0.01, P = 0.04) but not Hbmass (B = 0.10, P = 0.41). During HA, PV increased 8.2% (P < 0.01), while Hbmass, CTL and ATL were unchanged. Hbmass and [Hb] were associated with all performance outcomes (P < 0.05), except V̇O2max. PV and BV were not associated with performance outcomes. During temperate training, changes in Hbmass were most strongly associated with changes in CTL. Both CTL and ATL were associated with changes in PV, but HA was associated with increased PV and maintenance of Hbmass without increasing ATL or CTL. In practical terms, maintaining high CTL and high Hbmass might be beneficial for improving endurance performance.HIGHLIGHTSChanges in haemoglobin mass were associated with endurance exercise performance and changes in chronic training load in temperate conditions.Heat acclimation increased plasma volume and maintained haemoglobin mass independently of chronic training load.Chronic training loads and haemoglobin mass should be increased to improve endurance exercise performance.Heat acclimation may optimise haematological adaptations when training load is reduced.

Noninvasive Monitoring of Simulated Hemorrhage and Whole Blood Resuscitation.

Hemorrhage is the leading cause of preventable death from trauma. Accurate monitoring of hemorrhage and resuscitation can significantly reduce mortality and morbidity but remains a challenge due to the low sensitivity of traditional vital signs in detecting blood loss and possible hemorrhagic shock. Vital signs are not reliable early indicators because of physiological mechanisms that compensate for blood loss and thus do not provide an accurate assessment of volume status. As an alternative, machine learning (ML) algorithms that operate on an arterial blood pressure (ABP) waveform have been shown to provide an effective early indicator. However, these ML approaches lack physiological interpretability. In this paper, we evaluate and compare the performance of ML models trained on nine ABP-derived features that provide physiological insight, using a database of 13 human subjects from a lower-body negative pressure (LBNP) model of progressive central hypovolemia and subsequent progressive restoration to normovolemia (i.e., simulated hemorrhage and whole blood resuscitation). Data were acquired at multiple repressurization rates for each subject to simulate varying resuscitation rates, resulting in 52 total LBNP collections. This work is the first to use a single ABP-based algorithm to monitor both simulated hemorrhage and resuscitation. A gradient-boosted regression tree model trained on only the half-rise to dicrotic notch (HRDN) feature achieved a root-mean-square error (RMSE) of 13%, an R2 of 0.82, and area under the receiver operating characteristic curve of 0.97 for detecting decompensation. This single-feature model's performance compares favorably to previously reported results from more-complex black box machine learning models. This model further provides physiological insight because HRDN represents an approximate measure of the delay between the ABP ejected and reflected wave and therefore is an indication of cardiac and peripheral vascular mechanisms that contribute to the compensatory response to blood loss and replacement.

Observational study on passive leg raising and the autonomic nervous system.

In the intensive care and perioperative setting, circulation is often supported by intravenous fluid preceded by prediction of fluid responsiveness during a passive leg raising (PLR) maneuver. An increase in stroke volume (SV) or cardiac output (CO) of 10%-15% indicates that the subject may increase the flow upon volume expansion. However, the semi-recumbent position as an initial position in PLR likely reduces SV by gravitational displacement of central blood volume (CBV) to lower extremities, thereby accentuating volume responsiveness during leg raising in healthy people. Coincident with gravitational perturbations in hemodynamics, remedial changes occur in the autonomic nervous system (ANS), as expressed in spectral power in heart rate variability (HRV). This study aims to clarify these concomitant changes during PLR. A convenience number of healthy volunteers (N = 11) were recruited by advertisement in university departments. The subjects were exposed to the established PLR sequence and the heart rate (HR), mean arterial pressure (MAP), SV, and CO were sampled at 1 Hz, while electrocardiogram was recorded at 1000 Hz. Relative powers reflecting autonomic nervous system activity were assessed from spectral analysis of HRV. In response to PLR, SV increased (12.4% ± 8.7%, p < 0.0026), while HR (-7.6% ± 4.7%, p < 0.0009) and MAP (-7.6% ± 6.9%, p < 0.01) decreased, with no change in CO (4.1% ± 12.8%, ns). The HRV low-frequency component was reduced (-34%; p < 0.0095), while the high-frequency activity increased (78.5%; p < 0.0013), with a 63% decrease in the low/high frequency ratio (p < 0.0078). Thus, HRV indicated a reduced sympathetic index (semi-recumbent 0.808 vs. PLR -0.177 a.u., p < 0.001) and an increased parasympathetic index (-0.141 to 0.996 a.u., p < 0.0001). Gravitational depletion and expansion of CBV during PLR were associated with a counterregulatory autonomic response. Healthy volunteers appeared volume responsive in terms of SV, but not CO. Responses to PLR are influenced by the ANS, and HRV analysis should be included in the assessment of the PLR test.

Whole-brain perfusion mapping in mice by dynamic BOLD MRI with transient hypoxia.

Non-invasive mapping of cerebral perfusion is critical for understanding neurovascular and neurodegenerative diseases. However, perfusion MRI methods cannot be easily implemented for whole-brain studies in mice because of their small size. To overcome this issue, a transient hypoxia stimulus was applied to induce a bolus of deoxyhemoglobins as an endogenous paramagnetic contrast in blood oxygenation level-dependent (BOLD) MRI. Based on stimulus-duration-dependent studies, 5 s anoxic stimulus was chosen, which induced a decrease in arterial oxygenation to 59%. Dynamic susceptibility changes were acquired with whole-brain BOLD MRI using both all-vessel-sensitive gradient-echo and microvascular-sensitive spin-echo readouts. Cerebral blood flow (CBF) and cerebral blood volume (CBV) were quantified by modeling BOLD dynamics using a partial-volume-corrected arterial input function. In the mouse under ketamine/xylazine anesthesia, total CBF and CBV were 112.0 ± 15.0 ml/100 g/min and 3.39 ± 0.59 ml/100 g (n = 15 mice), respectively, whereas microvascular CBF and CBV were 85.8 ± 6.9 ml/100 g/min and 2.23 ± 0.27 ml/100 g (n = 7 mice), respectively. Regional total vs. microvascular perfusion metrics were highly correlated but a slight mismatch was observed in the large-vessel areas and cortical depth profiles. Overall, this non-invasive, repeatable, simple hypoxia BOLD-MRI approach is viable for perfusion mapping of rodents.

To identify normovolemia in humans: The stroke volume response to passive leg raising vs. head-down tilt.

Volume responsiveness can be evaluated by tilting maneuvers such as head-down tilt (HDT) and passive leg raising (PLR), but the two procedures use different references (HDT the supine position; PLR the semi-recumbent position). We tested whether the two procedures identify "normovolemia" by evaluating the stroke volume (SV) and cardiac output (CO) responses and whether the peripheral perfusion index (PPI) derived from pulse oximetry provides similar information. In randomized order, 10 healthy men were exposed to both HDT and PLR, and evaluations were made also when the subjects fasted. Central cardiovascular variables were derived by pulse contour analysis and changes in central blood volume assessed by thoracic electrical admittance (TEA). During HDT, SV remained stable (fasted 110 ± 16 vs. 109 ± 16 ml; control 113 ± 16 vs. 111 ± 16 ml, p > 0.05) with no change in CO, TEA, PPI, or SV variation (SVV). In contrast during PLR, SV increased (fasted 108 ± 17 vs. 117 ± 17 ml; control 108 ± 18 vs. 117 ± 18 ml, p < 0.05) followed by an increase in TEA (p < 0.05) and CO increased when subjects fasted (6.7 ± 1.5 vs. 7.1 ± 1.5, p = 0.007) with no change in PPI or SVV. In conclusion, SV has a maximal value for rest in supine men, while PLR restores SV as CBV is reduced in a semi-recumbent position and the procedure thereby makes healthy volunteers seem fluid responsive.

Myocardial Tissue Oxygenation and Microvascular Blood Volume Measurement Using a Contrast Blood Oxygenation Level-Dependent Imaging Model.

OBJECTIVES: We propose a method of quantitatively measuring drug-induced microvascular volume changes, as well as drug-induced changes in blood oxygenation using calibrated blood oxygen level-dependent magnetic resonance imaging (MRI). We postulate that for MRI signals there is a contribution to R2* relaxation rates from static susceptibility effects of the intravascular blood that scales with the blood volume/magnetic field and depends on the oxygenation state of the blood. These may be compared with the effects of an intravascular contrast agent. With 4 R2* measurements, microvascular blood volume (MBV) and tissue oxygenation changes can be quantified with the administration of a vasoactive drug. MATERIALS AND METHODS: The protocol examined 12 healthy rats in a prospective observational study. R2* maps were acquired with and without infusion of adenosine, which increases microvascular blood flow, or dobutamine, which increases myocardial oxygen consumption. In addition, R2* maps were acquired after the intravenous administration of a monocrystalline iron oxide nanoparticle, with and without adenosine or dobutamine. RESULTS: Total microvascular volume was shown to increase by 10.8% with adenosine and by 25.6% with dobutamine ( P < 0.05). When comparing endocardium versus epicardium, both adenosine and dobutamine demonstrated significant differences between endocardial and epicardial MBV changes ( P < 0.05). Total myocardial oxygenation saturation increased by 6.59% with adenosine and by 1.64% with dobutamine ( P = 0.27). The difference between epicardial and endocardial oxygenation changes were significant with each drug (adenosine P < 0.05, dobutamine P < 0.05). CONCLUSIONS: Our results demonstrate the ability to quantify microvascular volume and oxygenation changes using calibrated blood oxygen level-dependent MRI, and we demonstrate different responses of adenosine and dobutamine. This method has clinical potential in examining microvascular disease in various disease states without the administration of radiopharmaceuticals or gadolinium-based contrast agents.

AI-Enabled Advanced Development for Assessing Low Circulating Blood Volume for Emergency Medical Care: Comparison of Compensatory Reserve Machine-Learning Algorithms.

The application of artificial intelligence (AI) has provided new capabilities to develop advanced medical monitoring sensors for detection of clinical conditions of low circulating blood volume such as hemorrhage. The purpose of this study was to compare for the first time the discriminative ability of two machine learning (ML) algorithms based on real-time feature analysis of arterial waveforms obtained from a non-invasive continuous blood pressure system (Finometer®) signal to predict the onset of decompensated shock: the compensatory reserve index (CRI) and the compensatory reserve metric (CRM). One hundred ninety-one healthy volunteers underwent progressive simulated hemorrhage using lower body negative pressure (LBNP). The least squares means and standard deviations for each measure were assessed by LBNP level and stratified by tolerance status (high vs. low tolerance to central hypovolemia). Generalized Linear Mixed Models were used to perform repeated measures logistic regression analysis by regressing the onset of decompensated shock on CRI and CRM. Sensitivity and specificity were assessed by calculation of receiver-operating characteristic (ROC) area under the curve (AUC) for CRI and CRM. Values for CRI and CRM were not distinguishable across levels of LBNP independent of LBNP tolerance classification, with CRM ROC AUC (0.9268) being statistically similar (p = 0.134) to CRI ROC AUC (0.9164). Both CRI and CRM ML algorithms displayed discriminative ability to predict decompensated shock to include individual subjects with varying levels of tolerance to central hypovolemia. Arterial waveform feature analysis provides a highly sensitive and specific monitoring approach for the detection of ongoing hemorrhage, particularly for those patients at greatest risk for early onset of decompensated shock and requirement for implementation of life-saving interventions.

The venous system during pregnancy. Part 1: physiologic considerations.

An essential contributor to the hemodynamic responses observed during pregnancy, the venous system is affected by hormones, blood volume, flow rates, and an enlarging uterus. The venous system is a dynamic reservoir for blood volume, within which a virtual point of conversion between unstressed volume (Vu) and stressed volume (Vs) exists. The physiologic importance of the venous system during pregnancy is best understood when the basic concepts, functional characteristics, and alterations in pregnancy are reviewed.