Residual volume fraction during walking using wireless air plethysmography in patients with chronic deep venous disease.

OBJECTIVE: Traditional air plethysmography (APG) provides a quantitative measure of the residual volume fraction (RVF) after 10 tiptoe movements. The recent development of a wireless Bluetooth (Bluetooth SIG, Inc, Kirkland, Wash) APG device, the PicoFlow (Microlab Elettronica, Padua, Italy), enabled us to measure RVF during normal walking. The aim of our study was to compare the RVF obtained during tiptoeing with RVF obtained during normal walking in patients with deep venous pathology (ie, reflux and/or obstruction). METHODS: A total of 61 consecutive symptomatic patients (27 women and 34 men; median age, 46 years; range, 18-79 years) with chronic venous disease due to deep venous pathology (venous reflux or obstruction, or both) before treatment or persisting after intervention were included in the present study. Of the 122 total limbs examined, 79 were affected by deep chronic venous disease and 43 contralateral limbs were normal with normal deep veins and acted as controls. The APG examination was performed using the PicoFlow device using the standard examination technique. The RVF was calculated from the residual volume at the end of 10 tiptoe movements and also during normal walking. RESULTS: At the end of the 10 tiptoe movements, the mean ± standard deviation RVF was 27.0% ± 13.2% in the limbs with normal deep veins and 38.8% ± 16.9% in the limbs with deep chronic venous disease (P < .001). During walking, when a steady state in volume was reached, the RVF was 26.3% ± 17.8% in the limbs with normal deep veins and 43.1% ± 18.6% in limbs with deep venous disease (P < 0.001). A significant difference was found between limbs with normal deep veins and limbs with deep venous reflux, irrespective of which exercise was performed. However, the mean RVF between the limbs with normal deep veins and those with outflow obstruction in the absence of reflux was significant during walking (P = .012) but not during tiptoeing (P = .212). The mean RVF was higher in the C3 to C6 limbs than in the C0 to C2 limbs with tiptoeing (29.9% ± 14.5% vs 38.3% ± 17.0%; P < .006). Similar results were obtained with walking (29.2% ± 18.0% vs 42.4% ± 18.8%; P < .004). CONCLUSIONS: In limbs with normal deep veins and deep veins with reflux, the RVF measured during walking with wireless APG was similar to the RVF obtained during tiptoeing. However, in the limbs with outflow obstruction in the absence of reflux, the RVF during walking was higher than the RVF after tiptoeing. Our results have shown that the evaluation of RVF during walking is feasible and practical.

Perfusion-guided sonopermeation of neuroblastoma: a novel strategy for monitoring and predicting liposomal doxorubicin uptake in vivo.

Neuroblastoma (NB) is the most common extracranial solid tumor in infants and children, and imposes significant morbidity and mortality in this population. The aggressive chemoradiotherapy required to treat high-risk NB results in survival of less than 50%, yet is associated with significant long-term adverse effects in survivors. Boosting efficacy and reducing morbidity are therefore key goals of treatment for affected children. We hypothesize that these may be achieved by developing strategies that both focus and limit toxic therapies to the region of the tumor. One such strategy is the use of targeted image-guided drug delivery (IGDD), which is growing in popularity in personalized therapy to simultaneously improve on-target drug deposition and assess drug pharmacodynamics in individual patients. IGDD strategies can utilize a variety of imaging modalities and methods of actively targeting pharmaceutical drugs, however in vivo imaging in combination with focused ultrasound is one of the most promising approaches already being deployed for clinical applications. Over the last two decades, IGDD using focused ultrasound with "microbubble" ultrasound contrast agents (UCAs) has been increasingly explored as a method of targeting a wide variety of diseases, including cancer. This technique, known as sonopermeation, mechanically augments vascular permeability, enabling increased penetration of drugs into target tissue. However, to date, methods of monitoring the vascular bioeffects of sonopermeation in vivo are lacking. UCAs are excellent vascular probes in contrast-enhanced ultrasound (CEUS) imaging, and are thus uniquely suited for monitoring the effects of sonopermeation in tumors. Methods: To monitor the therapeutic efficacy of sonopermeation in vivo, we developed a novel system using 2D and 3D quantitative contrast-enhanced ultrasound imaging (qCEUS). 3D tumor volume and contrast enhancement was used to evaluate changes in blood volume during sonopermeation. 2D qCEUS-derived time-intensity curves (TICs) were used to assess reperfusion rates following sonopermeation therapy. Intratumoral doxorubicin (and liposome) uptake in NB was evalauted ex vivo along with associated vascular changes. Results: In this study, we demonstrate that combining focused ultrasound therapy with UCAs can significantly enhance chemotherapeutic payload to NB in an orthotopic xenograft model, by improving delivery and tumoral uptake of long-circulating liposomal doxorubicin (L-DOX) nanoparticles. qCEUS imaging suggests that changes in flow rates are highly sensitive to sonopermeation and could be used to monitor the efficacy of treatment in vivo. Additionally, initial tumor perfusion may be a good predictor of drug uptake during sonopermeation. Following sonopermeation treatment, vascular biomarkers show increased permeability due to reduced pericyte coverage and rapid onset of doxorubicin-induced apoptosis of NB cells but without damage to blood vessels. Conclusion: Our results suggest that significant L-DOX uptake can occur by increasing tumor vascular permeability with microbubble sonopermeation without otherwise damaging the vasculature, as confirmed by in vivo qCEUS imaging and ex vivo analysis. The use of qCEUS imaging to monitor sonopermeation efficiency and predict drug uptake could potentially provide real-time feedback to clinicians for determining treatment efficacy in tumors, leading to better and more efficient personalized therapies. Finally, we demonstrate how the IGDD strategy outlined in this study could be implemented in human patients using a single case study.

Clinical Application of Apheresis in Very Small Dogs Weighing <8 kg to Pediatric Patients.

Apheresis in low body weight children and adolescents is challenging due to a variety of technical and clinical issues including vascular access, low total blood volume, and hypotension. Although dogs have been a valuable preclinical model for apheresis, the procedure can be challenging since many pure-bred dogs are extremely small. Therefore, apheresis in these very small breeds presents very similar challenges as seen when performing the procedure in very low body weight people. We describe apheresis of four very small dogs, weighing from 4.6 to 7.6 kg, using either a COBESpectra and Spectra Optia apheresis system (Terumo BCT, Lakewood, CO, USA). Two dogs underwent large volume leukapheresis to collect mononuclear cells in preparation for hematopoietic stem cell transplantation and two dogs underwent therapeutic plasma exchange to treat an immune-mediated disease. In all cases, a dual-lumen hemodialysis catheter placed in the jugular vein provided adequate machine inlet and return flow rates. Machine priming was necessary to maintain hemodynamic stability during the beginning of the procedure, and rinseback was avoided for the same reason. Anticoagulant citrate dextrose solution, solution A was used for the large volume leukapheresis procedures and a combination of anticoagulant citrate dextrose solution, solution A and heparin was used for the therapeutic plasma exchange procedures. As such, serum iCa levels were regularly monitored and 10% calcium gluconate constant rate infusions were used to prevent citrate toxicity. All dogs completed the aphereses with no life-threatening adverse events. We conclude that aphereses in very small dogs is feasible if close attention is paid to hemodynamic stability and citrate toxicity.

Vascular Pressure-Flow Measurement Using CB-PDMS Flexible Strain Sensor.

Regular monitoring of blood flow and pressure in vascular reconstructions or grafts would provide early warning of graft failure and improve salvage procedures. Based on biocompatible materials, we have developed a new type of thin, flexible pulsation sensor (FPS) which is wrapped around a graft to monitor blood pressure and flow. The FPS uses carbon black (CB) nanoparticles dispersed in polydimethylsiloxane (PDMS) as a piezoresistive sensor layer, which was encapsulated within structural PDMS layers and connected to stainless steel interconnect leads. Because the FPS is more flexible than natural arteries, veins, and synthetic vascular grafts, it can be wrapped around target conduits at the time of surgery and remain implanted for long-term monitoring. In this study, we analyze strain transduction from a blood vessel and characterize the electrical and mechanical response of CB-PDMS from 0-50% strain. An optimum concentration of 14% CB-PDMS was used to fabricate 300-µm thick FPS devices with elastic modulus under 500 kPa, strain range of over 50%, and gauge factor greater than 5. Sensors were tested in vitro on vascular grafts with flows of 0-1,100 mL/min. In vitro testing showed linear output to pulsatile flows and pressures. Cyclic testing demonstrated robust operation over hundreds of cardiac cycles, with ±2.6 mmHg variation in pressure readout. CB-PDMS composite material showed excellent potential in biologic strain sensing applications where a flexible sensor with large maximum strain range is needed.

Utility of Percentage Signal Recovery and Baseline Signal in DSC-MRI Optimized for Relative CBV Measurement for Differentiating Glioblastoma, Lymphoma, Metastasis, and Meningioma.

BACKGROUND AND PURPOSE: The percentage signal recovery in non-leakage-corrected (no preload, high flip angle, intermediate TE) DSC-MR imaging is known to differ significantly for glioblastoma, metastasis, and primary CNS lymphoma. Because the percentage signal recovery is influenced by preload and pulse sequence parameters, we investigated whether the percentage signal recovery can still differentiate these common contrast-enhancing neoplasms using a DSC-MR imaging protocol designed for relative CBV accuracy (preload, intermediate flip angle, low TE). MATERIALS AND METHODS: We retrospectively analyzed DSC-MR imaging of treatment-naïve, pathology-proved glioblastomas (n = 14), primary central nervous system lymphomas (n = 7), metastases (n = 20), and meningiomas (n = 13) using a protocol designed for relative CBV accuracy (a one-quarter-dose preload and single-dose bolus of gadobutrol, TR/TE = 1290/40 ms, flip angle = 60° at 1.5T). Mean percentage signal recovery, relative CBV, and normalized baseline signal intensity were compared within contrast-enhancing lesion volumes. Classification accuracy was determined by receiver operating characteristic analysis. RESULTS: Relative CBV best differentiated meningioma from glioblastoma and from metastasis with areas under the curve of 0.84 and 0.82, respectively. The percentage signal recovery best differentiated primary central nervous system lymphoma from metastasis with an area under the curve of 0.81. Relative CBV and percentage signal recovery were similar in differentiating primary central nervous system lymphoma from glioblastoma and from meningioma. Although neither relative CBV nor percentage signal recovery differentiated glioblastoma from metastasis, mean normalized baseline signal intensity achieved 86% sensitivity and 50% specificity. CONCLUSIONS: Similar to results for non-preload-based DSC-MR imaging, percentage signal recovery for one-quarter-dose preload-based, intermediate flip angle DSC-MR imaging differentiates most pair-wise comparisons of glioblastoma, metastasis, primary central nervous system lymphoma, and meningioma, except for glioblastoma versus metastasis. Differences in normalized post-preload baseline signal for glioblastoma and metastasis, reflecting a snapshot of dynamic contrast enhancement, may motivate the use of single-dose multiecho protocols permitting simultaneous quantification of DSC-MR imaging and dynamic contrast-enhanced MR imaging parameters.

C-arm cone-beam CT parenchymal blood volume imaging for transarterial chemoembolization of hepatocellular carcinoma: implications for treatment planning and response.

We report on the feasibility of C-arm cone-beam computed tomography (CBCT) parenchymal blood volume imaging (PBVI) performed immediately following transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) to assess the need for repeat treatment. Eighteen TACE procedures were included. A retrospective assessment was made for the presence or absence of residual disease requiring treatment on immediate post-TACE PBVI and on interval follow-up multidetector computed tomography (MDCT) or magnetic resonance imaging (MRI). In 9/18 cases, both PBVI and MDCT/MRI showed that no further treatment was required. In 6/18 cases, further treatment was required on both PBVI and MDCT/MRI. In three cases, PBVI showed that further treatment was not required but MDCT/MRI showed residual disease requiring repeat treatment. There were no cases with PBVI showing residual disease not detected on follow-up MDCT/MRI. The PBVI sensitivity for detecting disease requiring repeat TACE was 67% (95% confidence interval [CI] 30-93%), and specificity was 100% (95% CI 66-100%). The use of C-arm CBCT PBVI for the detection of residual viable tumor within a treated lesion immediately after TACE is feasible. It may allow repeat TACE to be planned without performing interval imaging with MDCT or MRI.

Can cone-beam CT tumor blood volume predicts the response to chemoembolization of colorectal liver metastases? Results of an observational study.

PURPOSE: To determine whether intraprocedural C-arm cone-beam CT (CBCT) parenchymal blood volume (PBV) can predict the response of colorectal cancer liver metastases (CRCLM) 2 months after irinotecan drug-eluting bead (DEBIRI) chemoembolization. MATERIALS AND METHODS: This single-center observational study was compliant with the Helsinki Declaration and approved by our institutional review board. Thirty-four consecutive CRCLM patients referred for DEBIRI chemoembolization were enrolled between March 2015 and December 2016. Tumor size was assessed at baseline and 2 months after DEBIRI chemoembolization by multidetector CT (Response Evaluation Criteria in Solid Tumors RECIST 1.0), and PBV was measured before and after DEBIRI chemoembolization. Two independent readers reviewed all data. We determined the potential correlation (Spearman's rank correlation) between intraprocedural PBV values and tumor response at 2 months. The relationship between tumor response and PBV was studied using a mixed model. A logistic regression model was applied to study the relationship between patient "Responder/Non-responder" and PBV. RESULTS: There was a strong correlation between baseline PBV or the percent change of PBV and the 2-month tumor response (rho = - 0.8587 (p = 0.00001) and rho = 0.8027 (p = 0.00001), respectively). The mixed model showed that an increase of 1 ml/1000 ml in PBV of a tumor before DEBIRI chemoembolization led to a 0.54 mm decrease in diameter (p < 0.005). A 1% decrease in PBV after DEBIRI chemoembolization resulted in tumor shrinkage of 0.75 mm (p < 0.005). The logistic regression model showed that patients with a 1% smaller mean decrease of PBV after DEBIRI chemoembolization had a 10% lower likelihood of achieving disease control (OR = 0.9, 95% confidence interval (CI) = 0.81-1; p = 0.0493). CONCLUSION: Intraprocedural PBV may predict tumor response to DEBIRI chemoembolization. KEY POINTS: • There is a strong relationship between the parenchymal blood volume (PBV) of colorectal liver metastases before DEBIRI chemoembolization and tumor response at 2 months. • Higher PBV values before DEBIRI chemoembolization correlate with greater tumor shrinkage, but only if the PBV decreases by more than 70% after DEBIRI chemoembolization. • Each increase of 1% in the mean decrease of PBV after DEBIRI chemoembolization resulted in a 10% lower likelihood of achieving disease control (OR = 0.9, 95% confidence interval (CI) = 0.81-1; p = 0.0493).

Greater blood volume and Hb mass in obese women quantified by the carbon monoxide-rebreathing method affects interpretation of iron biomarkers and iron requirements.

BACKGROUND/OBJECTIVE: Iron deficiency (ID) is common in overweight and obese individuals (OW/OB) but the mechanism is uncertain. Greater blood volume (BV) in OW/OB may increase hemoglobin (Hb) mass and iron requirements, and confound iron biomarkers by hemodilution. Quantification of BV/PV changes in OW/OB is challenging and a formula to estimate BV/PV based on anthropometric indices would be valuable. In normal weight (NW) and OW/OB women, we aimed at: (1) measure BV and assess whether differences in BV affect concentrations and total circulating mass of Hb and iron biomarkers; (2) develop an algorithm describing BV in OW/OB. SUBJECTS/METHODS: In a cross-sectional study, we measured BV in NW, OW, and OB non-anemic women (n = 62) by using the carbon monoxide-rebreathing method, body composition by dual energy X-ray absorptiometry, and iron and inflammatory status. RESULTS: OW and OB women had 11 and 16% higher mean BV and PV compared to NW (P < 0.05), respectively. In OW/OB compared to NW, total circulating masses of IL-6, hepcidin, Hb, and sTfR were higher, while total mass of serum iron was lower (for all, P < 0.05). An equation including height, body mass and lean mass to estimate BV in all BMI groups (R2 = 0.76). CONCLUSION: An equation based on anthropometric indices provides a good estimate of increased BV in OW/OB women. In OW/OB women, there is an increase in Hb mass that likely increases iron requirements for erythropoiesis and circulating TfR mass. At the same time, higher hepcidin concentrations may lower serum iron mass. Both these mechanisms may increase risk for ID in OW/OB women.

Blood volume measurement using cardiovascular magnetic resonance and ferumoxytol: preclinical validation.

BACKGROUND: The hallmark of heart failure is increased blood volume. Quantitative blood volume measures are not conveniently available and are not tested in heart failure management. We assess ferumoxytol, a marketed parenteral iron supplement having a long intravascular half-life, to measure the blood volume with cardiovascular magnetic resonance (CMR). METHODS: Swine were administered 0.7 mg/kg ferumoxytol and blood pool T1 was measured repeatedly for an hour to characterize contrast agent extraction and subsequent effect on Vblood estimates. We compared CMR blood volume with a standard carbon monoxide rebreathing method. We then evaluated three abbreviated acquisition protocols for bias and precision. RESULTS: Mean plasma volume estimated by ferumoxytol was 61.9 ± 4.3 ml/kg. After adjustment for hematocrit the resultant mean blood volume was 88.1 ± 9.4 ml/kg, which agreed with carbon monoxide measures (91.1 ± 18.9 ml/kg). Repeated measurements yielded a coefficient of variation of 6.9%, and Bland-Altman repeatability coefficient of 14%. The blood volume estimates with abbreviated protocols yielded small biases (mean differences between 0.01-0.06 L) and strong correlations (r2 between 0.97-0.99) to the reference values indicating clinical feasibility. CONCLUSIONS: In this swine model, ferumoxytol CMR accurately measures plasma volume, and with correction for hematocrit, blood volume. Abbreviated protocols can be added to diagnostic CMR examination for heart failure within 8 min.

Evaluation of a multi-slice spiral computed tomography perfusion for the prediction of the recurrence of gastric cancer.

AIM: The study aimed to elucidate the value of multislice spiral computed tomography (MSCT) perfusion for the early prediction of gastric cancer (GC) recurrence. METHODS: MSCT perfusion scans were performed to obtain values pertaining to blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface (PS). Logistic regression analysis was employed to evaluate the risk factors of postoperative recurrence in GC. RESULTS: The maximum diameter of GC has a positive relationship with PS. The maximum enhancement of GC was positively correlated with BF, blood volume and PS. PS, BF, vascular thrombus and Tumor, Node, Metastasis staging were found to be significant risk factors in relation to the recurrence of GC (p = 0.006, p = 0.002, p < 0.001). CONCLUSION: MSCT perfusion is strongly correlated with postoperative recurrence of GC, and PS and BF values, vascular thrombus and Tumor, Node, Metastasis staging were discovered as being prominent factors influencing the recurrence of GC.

[Evaluation of the performance of a minimally invasive thoracic drainage tube in a rabbit model of hemothorax].

OBJECTIVE: To assess the performance of a minimally invasive thoracic drainage tube (14 F) made of polyurethane (PU) in a rabbit model of hemothorax in comparison with the conventional 28 F chest tube (CCT). METHODS: Thirty New Zealand rabbits were divided into experimental chest tube (ECT) group (n=9), CCT group (n=6), and blood provider group (n=15). Blood samples (20 mL) collected from the blood providing rabbits were injected into the chest cavity of the rabbits in the other two groups, and the time taken for closed drainage of the thoracic cavity was recorded. The rabbits in ECT and CCT groups were subjected to blood injections (20 mL for each injection) into the chest cavity every 20 min for 5 times, and the volumes of blood drained by ECT and CCT were measured. Two hours later, the rabbits were sacrificed and the residual blood and blood clots in the chest cavities were observed. RESULTS: Compared with CCT, the use of ECT significantly shortened the operation time (P<0.05) and produced more effective blood drainage at 20 min and 40 min after the placement of the drainage tube (P<0.05). No significant difference was found in the total blood volume drained between ECT and CCT groups, but the volume of residual blood in the thoracic cavity was significantly smaller in ECT group than in CCT group. No post-operative complications were found in the rabbits in ECT group while all the rabbits in CCT group had abutment pressure to the lung. CONCLUSION: Compared to CCT, ECT is less invasive and allows more effective thoracic drainage with more convenient operation and reduced postoperative complications, suggesting its potential for use in closed thoracic drainage in single-port video-assisted thoracoscopic surgery (VATS) or in pediatric patients.

Image quality of arterial phase and parenchymal blood volume (PBV) maps derived from C-arm computed tomography in the evaluation of transarterial chemoembolization.

BACKGROUND: To evaluate the benefits of arterial phase imaging and parenchymal blood volume (PBV) maps acquired by C-arm computed tomography during TACE procedure in comparison to cross-sectional imaging (CSI) using CT or MRI. METHODS: From January 2014 to December 2016, a total of 29 patients with HCC stage A or B (mean age 65 years; range 47 to 81 years, 86% male) were included in this study. These patients were referred to our department for TACE treatment and received peri-interventional C-arm CT. Dual phase findings of each lesion in terms of overall image quality, conspicuity, tumor size and feeding arteries were compared between arterial phase imaging and PBV using 5-point semi-quantitative Likert-scale, whereby pre-interventional CSI served as reference standard. RESULTS: A significantly higher overall image quality of the PBV maps compared to arterial phase C-arm CT acquisitions (4.34 (±0.55) vs. 3.93 (±0.59), p = 0.0032) as well as a higher conspicuity of HCC lesions (4.27 ± 0.74 vs. 3.83 ± 1.08, p < 0.0001) was observed. Arterial phase imaging led to an overestimation of tumor size (mean size, 26.5 ± 15.9 mm) compared to PBV (24.9 ± 15.2 mm, p = 0.0004) as well as CSI (25.2 ± 15.1 mm), p = 0.021). Regarding detectability of tumor feeding arterial vessels, significantly more feeding vessels were detected in arterial phase C-arm CT (n = 1.67 ± 0.92 vessels) compared to PBV maps (n = 1.27 ± 0.63 vessels) (p = 0.0001). One lesion was missed in pre-interventional CT imaging, but detected by C-arm CT. CONCLUSION: The combination of PBV maps and arterial phase images acquired by C-arm CT during TACE procedure enables precise detection of the majority of HCC lesions and tumor feeding arteries and has therefore the potential to improve patient outcome.

Intraprocedural Parenchymal Blood Volume Is a Predictor of Treatment Response for Chemoembolization in Hepatocellular Carcinoma: Results of a Prospective Study.

PURPOSE: To evaluate cone-beam parenchymal blood volume (PBV) before and after embolization as a predictor of radiographic response to transarterial chemoembolization in unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A phase IIa prospective clinical trial was conducted in patients with HCCs > 1.5 cm undergoing chemoembolization; 52 tumors in 40 patients with Barcelona Clinic Liver Criteria stage B disease met inclusion criteria. Pre- and postembolization PBV analysis was performed with a semiquantitative best-fit methodology for index tumors, with a predefined primary endpoint of radiographic response at 3 months. Analyses were conducted with Wilcoxon signed-rank tests and one-way analysis of variance on ranks. RESULTS: Mean tumoral PBV measurements before and after embolization were 170 mL/1,000 mL ± 120 and 0 mL/100 mL ± 130, respectively. Per modified Response Evaluation Criteria In Solid Tumors, 25 tumors (48%) exhibited complete response (CR), 13 (25%) partial response (PR), 3 (6%) stable disease (SD), and 11 (21%) progressive disease (PD). Statistically significant changes in median PBV (ΔPBV) were identified in the CR (P = .001) and PR (P = .003) groups, with no significant difference observed in SD (P = .30) and PD groups (P = .06). A statistically significant correlation between ΔPBV and tumor response was established by one-way analysis of variance on ranks (P = .036; CR, 200 mL/100 mL ± 99; PR, 240 mL/100 mL ± 370; SD, 64 mL/100 mL ± 99; PD, 88 mL/100 mL ± 129). CONCLUSIONS: Intraprocedural PBV can be used as a predictor of response in index HCC tumors of > 1.5 cm.

High-frequency oscillatory ventilation guided by transpulmonary pressure in acute respiratory syndrome: an experimental study in pigs.

BACKGROUND: Recent clinical studies have not shown an overall benefit of high-frequency oscillatory ventilation (HFOV), possibly due to injurious or non-individualized HFOV settings. We compared conventional HFOV (HFOVcon) settings with HFOV settings based on mean transpulmonary pressures (PLmean) in an animal model of experimental acute respiratory distress syndrome (ARDS). METHODS: ARDS was induced in eight pigs by intrabronchial installation of hydrochloric acid (0.1 N, pH 1.1; 2.5 ml/kg body weight). The animals were initially ventilated in volume-controlled mode with low tidal volumes (6 ml kg- 1) at three positive end-expiratory pressure (PEEP) levels (5, 10, 20 cmH2O) followed by HFOVcon and then HFOV PLmean each at PEEP 10 and 20. The continuous distending pressure (CDP) during HFOVcon was set at mean airway pressure plus 5 cmH2O. For HFOV PLmean it was set at mean PL plus 5 cmH2O. Baseline measurements were obtained before and after induction of ARDS under volume controlled ventilation with PEEP 5. The same measurements and computer tomography of the thorax were then performed under all ventilatory regimens at PEEP 10 and 20. RESULTS: Cardiac output, stroke volume, mean arterial pressure and intrathoracic blood volume index were significantly higher during HFOV PLmean than during HFOVcon at PEEP 20. Lung density, total lung volume, and normally and poorly aerated lung areas were significantly greater during HFOVcon, while there was less over-aerated lung tissue in HFOV PLmean. The groups did not differ in oxygenation or extravascular lung water index. CONCLUSION: HFOV PLmean is associated with less hemodynamic compromise and less pulmonary overdistension than HFOVcon. Despite the increase in non-ventilated lung areas, oxygenation improved with both regimens. An individualized approach with HFOV settings based on transpulmonary pressure could be a useful ventilatory strategy in patients with ARDS. Providing alveolar stabilization with HFOV while avoiding harmful distending pressures and pulmonary overdistension might be a key in the context of ventilator-induced lung injury.

Observer variability of reference tissue selection for relativecerebral blood volume measurements in glioma patients.

OBJECTIVES: To assess observer variability of different reference tissues used for relative CBV (rCBV) measurements in DSC-MRI of glioma patients. METHODS: In this retrospective study, three observers measured rCBV in DSC-MR images of 44 glioma patients on two occasions. rCBV is calculated by the CBV in the tumour hotspot/the CBV of a reference tissue at the contralateral side for normalization. One observer annotated the tumour hotspot that was kept constant for all measurements. All observers annotated eight reference tissues of normal white and grey matter. Observer variability was evaluated using the intraclass correlation coefficient (ICC), coefficient of variation (CV) and Bland-Altman analyses. RESULTS: For intra-observer, the ICC ranged from 0.50-0.97 (fair-excellent) for all reference tissues. The CV ranged from 5.1-22.1 % for all reference tissues and observers. For inter-observer, the ICC for all pairwise observer combinations ranged from 0.44-0.92 (poor-excellent). The CV ranged from 8.1-31.1 %. Centrum semiovale was the only reference tissue that showed excellent intra- and inter-observer agreement (ICC>0.85) and lowest CVs (<12.5 %). Bland-Altman analyses showed that mean differences for centrum semiovale were close to zero. CONCLUSION: Selecting contralateral centrum semiovale as reference tissue for rCBV provides the lowest observer variability. KEY POINTS: • Reference tissue selection for rCBV measurements adds variability to rCBV measurements. • rCBV measurements vary depending on the choice of reference tissue. • Observer variability of reference tissue selection varies between poor and excellent. • Centrum semiovale as reference tissue for rCBV provides the lowest observer variability.

Measurement of compensatory reserve predicts racial differences in tolerance to simulated hemorrhage in women.

BACKGROUND: The compensatory reserve measurement (CRM) has been established to accurately measure the body's total integrated capacity to compensate for physiologic states of reduced central blood volume and predict hemodynamic decompensation associated with inadequate tissue oxygenation. We previously demonstrated that African American (AA) women have a higher tolerance to reductions in central blood volume. Therefore, we tested the hypothesis that the CRM would identify racial differences during simulated hemorrhage, before the onset of traditional signs/symptoms. METHODS: We performed a retrospective analysis during simulated hemorrhage using lower-body negative pressure (LBNP) in 23 AA (22 ± 1 years; 24 ± 1 kg/m) and 31 white women (WW) (20 ± 1 years; 23 ± 1 kg/m). Beat-by-beat blood pressure (BP) and heart rate (HR) were recorded during progressive lower body negative pressure to presyncope. The BP waveforms were analyzed using a machine-learning algorithm to derive the CRM at each lower body negative pressure stage. RESULTS: Resting mean arterial BP (AA, 78 ± 3 mm Hg vs. WW, 74 ± 2 mm Hg) and HR (AA, 68 ± 2 bpm vs. WW, 65 ± 2 bpm) were similar between groups. The CRM progressively decreased during LBNP in both groups; however, the rate of decline in the CRM was less (p < 0.05) in AA. The CRM was 4% higher in AA at -15 mm Hg LBNP and progressively increased to 21% higher at -50 mm Hg LBNP (p < 0.05). However, changes in BP and HR were not different between groups. CONCLUSION: These data support the notion that the greater tolerance to simulated hemorrhage induced by LBNP in AA women can be explained by their greater capacity to protect the reserve to compensate for progressive central hypovolemia compared with WW, independent of standard vital signs. LEVEL OF EVIDENCE: Diagnostic test, level II.

The Assessment of Intravascular Volume with Inferior Vena Cava and Internal Jugular Vein Distensibility Indexes in Children Undergoing Urologic Surgery.

PURPOSE: The purpose of this work is to assess the predictive value, for fluid responsiveness (FR), of the inferior vena cava distensibility index (IVC-DI) and internal jugular vein distensibility index (IJV-DI) in pediatric surgical patients. MATERIAL AND METHODS: Prior to being placed under general anesthesia, 24 surgical patients were enrolled. Baseline parameters were recorded with the patient in the semirecumbent position (Stage 1). Next, the passive leg raising (PLR) maneuver was carried out and a second measurement was recorded (Stage 2). Patients with an increase in the cardiac index (CI) of >10%, induced by PLR, were considered to be responders (R), otherwise they were classified as nonresponders (NR). At both stages, CI and DI of the IVC and IJV were measured. RESULTS: Responders had higher IVC-DI and IVJ-DI than NR in stage 1 (both p <.001). In stage 2, IVC-DI and IJV-DI were not different in R and NR groups (p =.164, p =.201). Utilizing cut-off values of > 22.7% for IVC-DI and > 25% for IJV-DI, these parameters had positive correlation coefficients, both in R and NR of, respectively, 0.626 and 0.929. CONCLUSIONS: The IVC-DI predicts FR in anesthetized pediatric patients and correlates well with the IJV-DI; both may be used as prediction markers of FR in children.

Fluid Responsiveness After CArdiac Surgery (FRACAS): A Prospective Observational Study Using Peripheral Near-Infrared Spectroscopy.

OBJECTIVES: To describe tissue oxygen saturation (StO2) in response to a vascular occlusion test using thenar eminence and forearm near-infrared spectroscopy (NIRS) and the association with volume responsiveness after cardiac surgery. DESIGN: Single-center, prospective, observational cohort study. SETTING: Cardiothoracic intensive care unit. PARTICIPANTS: Seventy-six post-cardiac surgical adults. INTERVENTIONS: Immediately before and 10 minutes after a 250-to-500 mL fluid bolus, StO2 was measured in response to a vascular occlusion test to calculate tissue deoxygenation (Rdes) and reoxygenation (Rres) rates. Concurrently, systemic hemodynamic, metabolic, and blood gas variables were collected. MEASUREMENTS AND MAIN RESULTS: A total of 203 boluses were captured using thenar NIRS and 141 boluses using forearm NIRS. Approximately 25% of boluses increased cardiac output by ≥15% (volume responders). Thenar and forearm Rdes decreased in responders, but increased (thenar) or remained unchanged (forearm) in nonresponders. A logistic regression model of the association among StO2, Rdes and Rres, and volume responsiveness was significant for thenar measurements (p = 0.001) with an area under the receiver operating characteristic of 0.69 (95% confidence interval: 0.62-0.75). It also was significant (p = 0.02) for forearm measurements, with an area under the receiver operating characteristic of 0.71 (0.62-0.79). Rdes was an independent variable in both instances (odds ratio 0.31 [0.14-0.69], thenar; odds ratio 0.60 [0.45-0.80], forearm). Thenar and forearm NIRS variables were correlated poorly with cardiac output, stroke volume, systemic oxygen delivery and consumption index, mixed venous, and central venous oxygen saturation (Spearman׳s coefficients, r = 0.17-0.46, p < 0.002). CONCLUSION: In post-cardiac surgical patients, thenar and forearm NIRS variables were associated with volume responsiveness although not achieving precision necessary for clinical management.

Reliability and validity of non-invasive determined haemoglobin mass and blood volumes.

INTRODUCTION: The carbon monoxide (CO) rebreathing method used for the determination of haemoglobin mass (Hbmass ) is associated with blood sample analysis (in this study: Radiometer ABL800). As an alternative hereto the aim of the present study was to evaluate the use of a portable and non-invasive CO pulse oximeter (Rad-57). METHOD: With simultaneous determination of CO in the circulation by ABL800 (%HbCO) and Rad-57 (SpCO), Hbmass and blood volume (BV) were determined in duplicates in 24 volunteers. Percentage of typical errors (%TE) within methods and linear correlations between the two procedures were computed. RESULTS: Hbmass (Rad-57 = 798 ± 230 g; ABL800 = 781 ± 192 g) and BV (Rad-57 = 5700 ± 1373 ml; ABL800 = 5581 ± 1096 ml) were similar between methods. However, the %TE for Hbmass was higher (P<0·001) for Rad-57 (5·84 ± 5·29%) than for ABL800 (1·35 ± 1·13%). Similarly, the %TE for BV was higher (P<0·001) for Rad-57 (6·06 ± 5·76%) than for ABL800 (1·48 ± 1·25%). Lower (P<0·05) correlation coefficients between the methods were found when Hbmass  > 905 g and BV > 6193 ml. CONCLUSION: Assessment of SpCO by Rad-57 resulted in considerably less precise determinations of Hbmass and BV, especially for high values. Thus, non-invasive assessment of Hbmass and BV cannot be recommended for scientific purposes, but may nonetheless be useful in clinical settings.

Blood flow, volume and arterio-venous passages in induced mammary tumours of the rat.

OBJECTIVE: To study blood flow, vascular volume and arterio-venous passages in induced mammary tumours of the rat to characterize parameters possibly responsible for tumour hyponutrition. METHOD: Dimethylbenzanthracene-induced mammary tumours in Sprague-Dawley rats were studied. Regional blood flow was studied by use of the radioactive microsphere tracer technique using 141Cerium-labelled 15µm spheres coinjected into the left cardiac ventricle with 125Iodine-labelled 25µm spheres. Blood volume was studied by use of 125Iodine- or 99mTechnetium-labelled human serum albumin, the latter allowing autoradiography of tumour sections for visualization of flow and volume. RESULTS: Twenty-seven rats with 170 tumours had a mean tumour blood flow of 48 and 67mL×min-1×100g-1 using 15 and 25µm sphere data, respectively, indicating a significant passage through vessels between 15 and 25µm. The lungs showed a "nominal bronchial" blood flow of 260 and 135mL×min-1×100g-1 for the 15 and 25µm spheres, respectively, indicating pulmonary trapping, particularly of small spheres passing the systemic circulation in vessels larger than 15µm. There was a positive correlation between the total tumour blood flow within individual rats and trapped spheres of both dimensions in the lungs, indicating shunts also larger than 25µm. Normal tissues disclosed only small differences in regional blood flow as measured by the two spheres. Blood volume was studied in 20 rats with 120 tumours, with a vascular volume of 3.6mL×100g-1 representing a blood turnover >15 times/min. Blood volume co-localized with perfusion as seen in autoradiographs. CONCLUSION: In induced rat mammary tumours, a high fraction of blood, 28%, passes arterio-venous vessels between 15 and 25µm and there also exist passages >25µm. These findings indicate that the functional capacity of the tumour vascular bed might be impaired, adding to the abnormal microenvironment of tumours.