Relative Blood Volume Changes Research Articles

Value of dynamic contrast perfusion MRI to predict early response to bevacizumab in newly diagnosed glioblastoma: results from ACRIN 6686 multicenter trial.

In Radiation Therapy Oncology Group (RTOG) 0825, a phase III trial of standard therapy with bevacizumab or without (placebo) in newly diagnosed glioblastoma, 44 patients underwent dynamic contrast enhanced (DCE) and/or dynamic susceptibility contrast (DSC) MRI in the American College of Radiology Imaging Network (ACRIN) trial 6686. The association between early changes in relative cerebral blood volume (rCBV) and volume transfer constant (Ktrans) with overall survival (OS) was evaluated. MRI was performed at postop baseline (S0), immediately before (S1), 1 day after (S2), and 7 weeks after (S3) bevacizumab or placebo initiation. Mean normalized and standardized rCBV (nRCBV, sRCBV) and Ktrans were measured within contrast-enhancing lesion. Wilcoxon rank sum tests compared parameter changes from S1-S2 and S1-S3. Association with OS and progression-free survival (PFS) were determined using Kaplan-Meier and log-rank tests. Treatment response for groups stratified by pretreatment nRCBV (S0, S1) was explored. The intraclass correlation coefficient and repeatability coefficient for the placebo arm (S1-S2) were used to assess repeatability. Evaluable were 27-36 datasets per time point. Significant differences between treatment arms were found for changes in nRCBV and sRCBV from S1-S2 and S1-S3, and in Ktrans for S1-S3. Improved PFS (P = 0.05) but not OS (P = 0.46) was observed. High pretreatment rCBV predicted improved OS for bevacizumab-treated patients. Based on the intraclass correlation coefficient, sRCBV (0.92) was more repeatable than nRCBV (0.71) and Ktrans (0.75), consistent with repeatability coefficient values. Bevacizumab significantly changes rCBV but not Ktrans as early as 1 day posttreatment in newly diagnosed glioblastoma unrelated to outcomes. Improvements in clinical trial design to maximize rCBV benefit are indicated.

Neurochemical underpinning of hemodynamic response to neuropsychiatric drugs: A meta- and cluster analysis of preclinical studies

Functional magnetic resonance imaging (fMRI) is an extensively used method for the investigation of normal and pathological brain function. In particular, fMRI has been used to characterize spatiotemporal hemodynamic response to pharmacological challenges as a non-invasive readout of neuronal activity. However, the mechanisms underlying regional signal changes are yet unclear. In this study, we use a meta-analytic approach to converge data from microdialysis experiments with relative cerebral blood volume (rCBV) changes following acute administration of neuropsychiatric drugs in adult male rats. At whole-brain level, the functional response patterns show very weak correlation with neurochemical alterations, while for numerous brain areas a strong positive correlation with noradrenaline release exists. At a local scale of individual brain regions, the rCBV response to neurotransmitters is anatomically heterogeneous and, importantly, based on a complex interplay of different neurotransmitters that often exert opposing effects, thus providing a mechanism for regulating and fine tuning hemodynamic responses in specific regions.

Hemodialysis-induced changes in hematocrit, hemoglobin and total protein: Implications for relative blood volume monitoring.

BackgroundRelative blood volume (RBV) changes during hemodialysis (HD) are typically estimated based on online measurements of hematocrit, hemoglobin or total blood protein. The aim of this study was to assess changes in the above parameters during HD in order to compare the potential differences in the RBV changes estimated by individual methods.Methods25 anuric maintenance HD patients were monitored during a 1-week conventional HD treatment. Blood samples were collected from the arterial dialysis blood line at the beginning and at the end of each HD session. The analysis of blood samples was performed using the hematology analyzer Advia 2120 and clinical chemistry analyzer Advia 1800 (Siemens Healthcare).ResultsDuring the analyzed 30 HD sessions with ultrafiltration in the range 0.7–4.0 L (2.5 ± 0.8 L) hematocrit (HCT) increased by 9.1 ± 7.0% (mean ± SD), hemoglobin (HGB) increased by 10.6 ± 6.3%, total plasma protein (TPP) increased by 15.6 ± 9.5%, total blood protein (TBP) increased by 10.4 ± 5.8%, red blood cell count (RBC) increased by 10.8 ± 7.1%, while mean corpuscular red cell volume (MCV) decreased by 1.5 ± 1.1% (all changes statistically significant, p < 0.001). HGB increased on average by 1.5% more than HCT (p < 0.001). The difference between HGB and TBP increase was insignificant (p = 0.16).ConclusionsTracking HGB or TBP can be treated as equivalent for the purpose of estimating RBV changes during HD. Due to the reduction of MCV, the HCT-based estimate of RBV changes may underestimate the actual blood volume changes.

Transcapillary Refilling Rate and Its Determinants during Haemodialysis with Standard and High Ultrafiltration Rates

Background: Achieving euvolaemia using ultrafiltration (UF) during haemodialysis (HD) without inducing haemodynamic instability presents a major clinical challenge. Transcapillary refill is a key factor in sustaining the circulating blood volume (BV) during UF, which is in turn predicted by the rate of refilling. However, absolute plasma refilling rate (PRR), its determinants and variability with UF rate (UFR), have not been reported in the literature. Method: We studied paired HD sessions (n = 48) in 24 patients over 2 consecutive mid-week HD treatments. Plasma refilling was measured using real-time, minute-by-minute relative BV changes obtained from the integrated BV monitoring device during UF. A fixed bolus dilution approach at the start of HD was used to calculate absolute BV. The first control HD session was undertaken with a standard UFR required to achieve the prescribed target weight, while during the second study session, a fixed (high) UFR (1 L/h) was applied, either in the first (n = 12 patients) or in the final hour (n = 12 patients) of the HD session. Participants’ had their hydration status measured pre- and post-HD using multifrequency bioimpedance (BIS). Blood pressure was measured at 15-min intervals and blood samples were collected at 7 intervals during HD sessions. Results: The mean PRR during a standard 4-hr HD session was 4.3 ± 2.0 mL/kg/h and varied between 2 and 6 mL/kg/h. There was a mean time delay of 22 min (range 13.3–35.0 min) for onset of plasma refilling after the application of UF irrespective of standard or high UFRs. The maximum refilling occurred during the second hour of HD (mean max PRR 6.8 mL/kg/h). UFR (beta = 0.60, p < 0.01) and BIS derived pre-HD overhydration index (beta = 0.44, p = 0.01) were consistent, independent predictors of the mean PRR (R² = 0.49) in all HD sessions. At high UFRs, PRR exceeded 10 mL/kg/h. The total overall plasma refill contribution to UF volume was not significantly different between standard and high UF. During interventions no significant haemodynamic instability was observed in the study. Conclusion:We describe absolute transcapillary refilling rate and its profile during HD with UF. The findings provide the basis for the development of UF strategies to match varying PRRs during HD. An approach to fluid removal, which is tailored to patients’ refilling rates and capacity, provides an opportunity for more precision in the practice of UF.

Shining new light on mammalian diving physiology using wearable near-infrared spectroscopy.

Investigation of marine mammal dive-by-dive blood distribution and oxygenation has been limited by a lack of noninvasive technology for use in freely diving animals. Here, we developed a noninvasive near-infrared spectroscopy (NIRS) device to measure relative changes in blood volume and haemoglobin oxygenation continuously in the blubber and brain of voluntarily diving harbour seals. Our results show that seals routinely exhibit preparatory peripheral vasoconstriction accompanied by increased cerebral blood volume approximately 15 s before submersion. These anticipatory adjustments confirm that blood redistribution in seals is under some degree of cognitive control that precedes the mammalian dive response. Seals also routinely increase cerebral oxygenation at a consistent time during each dive, despite a lack of access to ambient air. We suggest that this frequent and reproducible reoxygenation pattern, without access to ambient air, is underpinned by previously unrecognised changes in cerebral drainage. The ability to track blood volume and oxygenation in different tissues using NIRS will facilitate a more accurate understanding of physiological plasticity in diving animals in an increasingly disturbed and exploited environment.

Body Fluids in End-Stage Renal Disease: Statics and Dynamics

Background: Abnormalities in fluid status in hemodialysis (HD) patients are highly prevalent and are related to adverse outcomes. Summary: The inherent discontinuity of the HD procedure in combination with an often compromised cardiovascular response is a major contributor to this phenomenon. In addition, systemic inflammation and endothelial dysfunction are related to extracellular fluid overload (FO). Underlying this relation may be factors such as hypoalbuminemia and an increased capillary permeability, leading to an altered fluid distribution between the blood volume (BV) and the interstitial fluid compartments, compromising fluid removal during dialysis. Indeed, whereas estimates of extracellular volume by bioimpedance spectroscopy are highly predictive of mortality, absolute BV assessed by the saline dilution technique was predictive of intra-dialytic morbidity. Changes in relative BV during HD are positively related to ultrafiltration rate (UFR) and, at least in some studies, negatively to FO. High UFR is also related to changes in central venous oxygen saturation (S_cvO₂), a marker for tissue perfusion. On the one hand, high UFR and more pronounced declines in S_cvO₂, but on the other hand, flat relative BV curves are also predictive of mortality; the relation between outcome which statics and dynamics of fluid status appears to be complex. Key Message: While technological developments enable the clinician to monitor statics and dynamics of fluid status and hemodynamics during HD in an accessible way, the role of technology-based interventions needs further study.

Time to Reconsider the Role of Relative Blood Volume Monitoring for Fluid Management in Hemodialysis.

Relative blood volume (RBV) monitoring during hemodialysis has been used to help guide fluid management for decades, although with little supporting evidence. The technique relies on the assumption that variation in RBV during fluid removal reflects the capacity for vascular refilling and that efficient refilling is related to fluid overload. This study investigated the relationship between RBV variation and bioimpedance-based fluid overload in 47 patients on stable hemodialysis. Mean treatment ultrafiltration volume (UFV) was 1.7 L and RBV reduction was 3.2%/hour. Relative blood volume slopes were grouped based on trajectory: flatline (no decrease), linear decrease, or linear decrease followed by flatline. Fluid overload was similar (p > 0.05) across groups pre-dialysis (1.0, 2.2, and 1.6 L, respectively) and post-dialysis (-0.8, -0.1, and -0.1 L), whereas UFV was higher in patients with a linear decrease (1.8, 2.5, and 1.6 L; p = 0.02). Specific ultrafiltration rate, but not fluid overload, was associated with RBV change over dialysis. At least half the patients in each group finished dialysis fluid depleted based on bioimpedance, suggesting that the link between refilling and fluid overload is not as straightforward as previously assumed. These results question the assumptions that the absence of an appreciable decrease in RBV indicates fluid overload, and a rapid fall suggests fluid depletion.

All-cause mortality in relation to changes in relative blood volume during hemodialysis.

BackgroundRelative blood volume (RBV) monitoring is widely used in hemodialysis (HD) patients, yet the association between intradialytic RBV and mortality is unknown.MethodsIntradialytic RBV was recorded once/min during a 6-month baseline period; all-cause mortality was noted during follow-up. RBV at 1, 2 and 3 h into HD served as a predictor of all-cause mortality during follow-up. We employed Kaplan–Meier analysis, univariate and adjusted Cox proportional hazards models for survival analysis.ResultsWe studied 842 patients. During follow-up (median 30.8 months), 249 patients (29.6%) died. The following hourly RBV ranges were associated with improved survival: first hour, 93–96% [hazard ratio (HR) 0.58 (95% confidence interval (CI) 0.42–0.79)]; second hour, 89–94% [HR 0.54 (95% CI 0.39–0.75)]; third hour, 86–92% [HR 0.46 (95% CI 0.33–0.65)]. In about one-third of patients the RBV was within these ranges and in two-thirds it was above. Subgroup analysis by median age (≤/> 61 years), sex, race (white/nonwhite), predialysis systolic blood pressure (SBP; ≤/> 130 mmHg) and median interdialytic weight gain (≤/> 2.3 kg) showed comparable favorable RBV ranges. Patients with a 3-h RBV between 86 and 92% were younger, had higher ultrafiltration volumes and rates, similar intradialytic average and nadir SBPs and hypotension rates, lower postdialysis SBP and a lower prevalence of congestive heart failure when compared with patients with an RBV >92%. In the multivariate Cox analysis, RBV ranges remained independent and significant outcome predictors.ConclusionSpecific hourly intradialytic RBV ranges are associated with lower all-cause mortality in chronic HD patients.

Dynamic Contrast-Enhanced Computed Tomography-Derived Blood Volume and Blood Flow Correlate With Patient Outcome in Metastatic Renal Cell Carcinoma.

The aim was to explore the potential for using dynamic contrast-enhanced computed tomography as a noninvasive functional imaging biomarker before and during the early treatment of metastatic renal cell carcinoma (mRCC). Dynamic contrast-enhanced computed tomography scans were performed at baseline and after 5 and 10 weeks' treatment in 69 prospectively included mRCC patients receiving treatment with interferon alpha and interleukin 2 (n = 26); interferon alpha, interleukin 2, and bevacizumab (n = 24); sunitinib (n = 7); pazopanib (n = 5); or temsirolimus (n = 7). Using a prototype software program (Advanced Perfusion and Permeability Application, Philips Healthcare, Best, the Netherlands), blood volume (BV), blood flow (BF), and permeability surface area product (PS) were calculated for each tumor at baseline, week 5, and week 10. These parameters as well as relative changes between baseline and weeks 5 and 10 were tested for associations with progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier curves and log-rank tests. Using the 25th percentile as the cutoff, baseline BV for all patients independent of subsequent treatment was statistically significantly associated with PFS (10.8 vs 5.3 months, P = 0.007) and OS (35.2 vs 13.3 months, P = 0.001), and baseline BF was significantly associated with OS (31.7 vs 14.6 months, P = 0.024) with high values for both parameters being associated with significantly longer PFS and OS. Baseline PS was not associated with PFS or OS.In patients treated with angiogenesis inhibitors (bevacizumab, sunitinib, pazopanib, or temsirolimus), the relative change in BV from baseline to week 5 using 25th percentile as the cutoff was associated with PFS (5.6 vs 24.8 months, P = 0.001) and OS (19.1 months vs not reached, P = 0.008) and from baseline to week 10 with PFS (8.1 vs 16.4 months, P = 0.014) and OS (15.5 months vs not reached, P = 0.002). The relative change in BF from baseline to week 5 using medians as the cutoff was associated with PFS (5.5 vs 14.3 months, P = 0.018) and OS (14.6 vs 31.7 months, P = 0.027). The relative change in BF from baseline to week 10 using 25th percentile as the cutoff was associated with PFS (8.3 vs 46.9 months, P = 0.011) and OS (19.1 vs 53.0 months, P = 0.006). For both parameters, the largest reductions during early treatment were associated with increased PFS and OS.In patients receiving immunotherapy only (interferon alpha and interleukin 2), relative changes in PS between baseline and weeks 5 and 10 were significantly associated with PFS with larger increases associated with longer PFS. In patients receiving angiogenesis inhibitors, the relative changes in PS between baseline and week 10 were significantly associated with PFS and OS with larger reductions associated with favorable outcomes. In patients with mRCC treated with angiogenesis inhibitors, the largest reductions in BV and BF between baseline and weeks 5 and 10 were associated with favorable outcomes. At baseline, the lowest BV and BF were associated with the poorest outcomes regardless of the subsequent treatment. Early reductions in PS were associated with favorable outcomes for those treated with angiogenesis inhibitors and with poor outcomes for those treated with immunotherapies.

Misleading early blood volume changes obtained using ferumoxytol-based magnetic resonance imaging perfusion in high grade glial neoplasms treated with bevacizumab.

BackgroundNeovascularization, a distinguishing trait of high-grade glioma, is a target for anti-angiogenic treatment with bevacizumab (BEV). This study sought to use ferumoxytol-based dynamic susceptibility contrast magnetic resonance imaging (MRI) to clarify perfusion and relative blood volume (rCBV) changes in glioma treated with BEV and to determine potential impact on clinical management.Methods16 high grade glioma patients who received BEV following post-chemoradiation radiographic or clinical progression were included. Ferumoxytol-based MRI perfusion measurements were taken before and after BEV. Lesions were defined at each timepoint by gadolinium-based contrast agent (GBCA)-enhancing area. Lesion volume and rCBV were compared pre and post-BEV in the lesion and rCBV “hot spot” (mean of the highest rCBV in a 1.08 cm2 area in the enhancing volume), as well as hypoperfused and hyperperfused subvolumes within the GBCA-enhancing lesion.ResultsGBCA-enhancing lesion volumes decreased 39% (P = 0.01) after BEV. Mean rCBV in post-BEV GBCA-enhancing area did not decrease significantly (P = 0.227) but significantly decreased in the hot spot (P = 0.046). Mean and hot spot rCBV decreased (P = 0.039 and 0.007) when post-BEV rCBV was calculated over the pre-BEV GBCA-enhancing area. Hypoperfused pixel count increased from 24% to 38 (P = 0.007) and hyperperfused decreased from 39 to 28% (P = 0.017). Mean rCBV decreased in 7/16 (44%) patients from >1.75 to <1.75, the cutoff for pseudoprogression diagnosis.ConclusionsDecreased perfusion after BEV significantly alters rCBV measurements when using ferumoxytol. BEV treatment response hinders efforts to differentiate true progression from pseudoprogression using blood volume measurements in malignant glioma, potentially impacting patient diagnosis and management.

Relative peripheral blood volume changes induced by premature ectopic beats and their role in hemodialysis

Hemodialysis patients often suffer from cardiovascular disorders and uremic neuropathy, increasing the propensity to homeostatic imbalance that, in turn, may result in intradialytic complications like cramp, nausea, and, worse, hypotension. Ectopic beats, being abundant in such patients, may lead to imbalance through repeated, sudden drops in blood pressure. By exploring the properties of postectopic peripheral circulation recovery, treatment sessions prone to intradialytic complications may be better identified. This paper introduces a novel method for quantifying changes in peripheral blood volume due to ventricular or supraventricular premature beats (VPBs or SVPBs). Using the fingertip photoplethysmographic pulse waveform, VPB and SVPB-induced changes in relative peripheral blood volume are quantified by the postectopic pulse amplitude. Two parameters are proposed for characterizing (i) the initial drop in peripheral blood volume following an ectopic beat, and (ii) the degree of postectopic peripheral circulation recovery. A small set of data from 16 hemodialysis sessions in 9 hypotension-prone patients are used to illustrate the method. In asymptomatic sessions, the first parameter was found to be 8 ± 13% (mean ± std), whereas, in symptomatic sessions, it increased to 32 ± 13%, suggesting that postectopic pulse amplitude recovery is related to intradialytic complications; similar results were obtained for the second parameter. Postectopic pulse amplitude recovery may also be of interest in other applications where relative changes in peripheral blood volume play a role.

Mapping the dynamics of brain perfusion using functional ultrasound in a rat model of transient middle cerebral artery occlusion

Following middle cerebral artery occlusion, tissue outcome ranges from normal to infarcted depending on depth and duration of hypoperfusion as well as occurrence and efficiency of reperfusion. However, the precise time course of these changes in relation to tissue and behavioral outcome remains unsettled. To address these issues, a three-dimensional wide field-of-view and real-time quantitative functional imaging technique able to map perfusion in the rodent brain would be desirable. Here, we applied functional ultrasound imaging, a novel approach to map relative cerebral blood volume without contrast agent, in a rat model of brief proximal transient middle cerebral artery occlusion to assess perfusion in penetrating arterioles and venules acutely and over six days thanks to a thinned-skull preparation. Functional ultrasound imaging efficiently mapped the acute changes in relative cerebral blood volume during occlusion and following reperfusion with high spatial resolution (100 µm), notably documenting marked focal decreases during occlusion, and was able to chart the fine dynamics of tissue reperfusion (rate: one frame/5 s) in the individual rat. No behavioral and only mild post-mortem immunofluorescence changes were observed. Our study suggests functional ultrasound is a particularly well-adapted imaging technique to study cerebral perfusion in acute experimental stroke longitudinally from the hyper-acute up to the chronic stage in the same subject.

Closed-Loop Fluid Resuscitation Control Via Blood Volume Estimation

This paper presents a closed-loop control of fluid resuscitation to overcome hypovolemia based on model-based estimation of relative changes in blood volume (BV). In this approach, the control system consists of a model-based relative BV (RBV) estimator and a feedback controller. The former predicts relative changes in the BV response to augmented fluid by analyzing an arterial blood pressure (BP) waveform and the electrocardiogram (ECG). Then, the latter determines the amount of fluid to be augmented by comparing target versus predicted relative changes in BV. In this way, unlike many previous methods for fluid resuscitation based on controlled variable(s) nonlinearly correlated with the changes in BV, fluid resuscitation can be guided by a controlled variable linearly correlated with the changes in BV. This paper reports initial design of the closed-loop fluid resuscitation system and its in silico evaluation in a wide range of hypovolemic scenarios. The results suggest that closed-loop fluid resuscitation guided by a controlled variable linearly correlated with the changes in BV can be effective in overcoming hypovolemia: across 100 randomly produced hypovolemia cases, it resulted in the BV regulation error of 7.98 ± 171.6 ml, amounting to 0.18 ± 3.04% of the underlying BV. When guided by pulse pressure (PP), a classical controlled variable nonlinearly correlated with the changes in BV; the same closed-loop fluid resuscitation system resulted in persistent under-resuscitation with the BV regulation error of −779.1 ± 147.4 ml, amounting to −13.9 ± 2.65% of the underlying BV.

Abstract IA11: Perfusion MRI: A potential biomarker of tumor response in clinical trials

Abstract This presentation will show an overview of perfusion MRI for in vivo imaging of solid cancers and emerging evidence supporting the use of this technique to monitor response to anticancer therapy is discussed. The noninvasive nature and high image resolution of Magnetic Resonance Imaging (MRI) makes it the preferred modality for in vivo imaging and disease monitoring of most solid cancers. While conventional MRI provides important anatomic information on the tumor and surrounding tissue, it reveals fewer insights on the metabolic and hemodynamic status and function of the tumor. With the advent of antiangiogenic agents that are not directly cytotoxic, there is an urgent need for clinical trials to incorporate advanced imaging analyses that goes beyond traditional and formalized imaging-based response criteria – usually by assessing tumor load after contrast agent administration. Blockade of vascular endothelial growth factors (VEGF) results in decreased vascular permeability and reduced tumor contrast enhancement on conventional MRI, artificially boosting radiographic response rates. Unfortunately, the high response rates do not always translate into prolonged survival [1]. The negative results of several recent late-phase trials suggest that first-line administration of antiangiogenic therapies in unselected patient groups is probably not the best approach, owing to diversity in cancer biology and natural history. Identification of a subset of cancer patients most likely to benefit from therapy and understanding the underlying mechanisms that separate these responding patients from non-responders are of high priority. According to the National Cancer Institute imaging response criteria [2], developing and validating clinical trial-acceptable advanced imaging methods can lead to smaller clinical trials with fewer patients by earlier and more-focused response assessments; faster regulatory approvals, and by this, earlier use of new drugs in clinical care. Dynamic contrast-enhanced MRI, or perfusion MRI, may help address the limitations of conventional imaging methods in antiangiogenic trials and complement these imaging exams with information on vascular permeability, blood flow and blood volume, among others. A large number of retrospective human studies show consistent reductions in abnormal vascular permeability after antiangiogenic therapy in a range of cancer types [3]. Small studies of brain tumor patients treated with VEGFR inhibitors also show a transient normalization of inefficient blood flow in a selected group of patients and suggest that vascular normalization may be a mechanism for improved delivery of adjuvant therapy and prolonged survival [4]. Similar data on changes in relative blood volume also show a sensitive, yet more complex response to VEGFR inhibition [5]. These efforts are followed by the recent introduction of MRI-based measurements of tumor vessel caliber and relative tissue oxygen saturation in clinical trial data [6]. These measurements are made possible using MR images sensitive to the vessel-size-related scale of magnetic field inhomogeneities created by blood and contrast agents flowing through the vessels. Most, if not all major manufacturers of MRI apparatus now provide these dedicated image protocols. Collectively, perfusion MRI may provide the clinical decision maker with a battery of complementary parameters capable of identifying the initial response, duration and end of the vascular remodeling period following antiangiogenic therapy and thereby enable early identification of patients most likely to benefit from targeted therapies.

Relative Blood Volume Monitoring during Renal Replacement Therapy in Critically Ill Patients with Septic Shock: A Preliminary Report

Background: Volume management during renal replacement therapy (RRT) in septic shock is always in the conflict between aggravating hypovolemia by undue ultrafiltration (UF) and insufficient reduction of fluid overload which is associated with adverse outcome. Relative blood volume (RBV) monitoring could be helpful for timely transition from fluid resuscitation to fluid removal. Methods: Data of RBV were continuously monitored and used for guidance of UF and fluid resuscitation in 21 consecutive patients with severe septic multiple organ failure. RRT was applied with extended daily hemodiafiltration for median 11 h (range 6-23). Changes in RBV were analyzed during the first 4 treatment sessions. Results: During 26 treatments, RBV monitoring revealed an internal volume loss substituted by a median infusion volume of 2.38 l (maximum 8.07 l) per treatment to keep the RBV constant. In the remaining 40 sessions, a median net-UF of 1.00 l (range 0.40-4.40) was achieved. In the first 2 days predominantly substitution was necessary whereas from the third day UF became increasingly possible. The 28-day survival rate was 81%. Conclusion: Blood volume monitoring proved to be an easy and feasible tool for safe guidance of fluid management maintaining the balance between UF and vascular refilling. Video Journal Club ‘Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=433415.

Kinetics of plasma refilling during hemodialysis sessions with different initial fluid status.

Removal of fluid excess from the plasma volume by ultrafiltration during hemodialysis (HD) is balanced by plasma refilling from the interstitium, driven mainly by the increase in plasma oncotic pressure. We calculated the plasma refilling coefficient (Kr, a parameter expressing the ratio of refilling rate to the increase in oncotic pressure) for nine patients, each undergoing two HD sessions differing by pretreatment fluid status and session time (shorter session, SH, 3.5 h, and longer session, LH, 4.5h). Relative blood volume change was measured online, and solute concentrations were measured regularly during the sessions. The volume of body compartments was measured by bioimpedance. The patients were more volume expanded before LH session (higher initial body mass and total body water). Oncotic pressure was similar for both sessions. The refilling rate, despite higher fluid overload in the LH sessions, was similar for both sessions. The final Kr values stabilized on similar levels (SH: 136.6 ± 55.6 ml/mm Hg/h and LH: 150.7 ± 73.6 ml/mm Hg/h) at similar times, notwithstanding the difference in initial fluid overload between the two groups, suggesting that Kr at dry weight is relatively insensitive to the initial fluid status of the patient.

VLSI Wavelet Based Denoising of PPG Signal

Wavelet denoising represents a common preprocessing step for several biomedical applications exposing low SNR. These applica- tions require real time processing along with minimization of power and area, only custom VLSI implementations can be adopted for this fulfillment. In this paper, Photoplethysmography (PPG) signal is used as a biomedical signal as an example. PPG is a non-invasive method in which relative blood volume changes in the blood close to skin is measured. The “pulse waveform” never underwent intensive investigation. Active investigation efforts are opening to reveal its effectiveness beyond oxygen saturation and determination of heart rate. With the introduction of pulse oximeter, this is one of the important waveforms that are normally dis- played in the clinical settings nowadays. But, the acquired PPG signal using PPG sensors are usually corrupted with different kinds of interference like Motion Artifacts, Power Line Noise, etc. We consider Power Line Noise for the performance evaluation of VLSI Wavelet based denoising of PPG signal. Different kinds of Wavelets such as db4, Coif1, Haar for denoising. Also, standard deviation and mean absolute deviation are used as evaluation criteria. Xilinx System Generator for DSP is exploited for the design of the architecture and simulation of proposed denoising method.

Comparison of Left and Right Fingertip PPG Signals Using Signal Power Estimates and Poincare Indexes

Photoplethysmography (PPG) is a non-invasive method to measure the relative blood volume change in blood vessels used in a wide range of medical applications. PPG signals can be recorded from different body regions such as fingertips, forehead and earlobes. In this study, information content of PPG signals of the left and the right index fingertips are processed and analyzed. PPG recordings are performed from ten healthy volunteers. Prior to recordings, all volunteers take rest for five minutes. Using a dedicated measurement system, signals are recorded from the left and the right fingertips of each volunteer simultaneously for 60 seconds with a sampling frequency of 50Hz, digitized with 10-bit resolution and stored in a personal computer. Signal average power and Poincare indexes of the signals are estimated and statistically analyzed. There are no systematic differences between the signal power estimated from the left and right fingertip signals (P>0.5). The signal power estimates for the left and the right fingertips show moderate correlations of 0.78, 0.80 and 0.68 for 0-4Hz, 0-2Hz and 2-4Hz frequency bands, respectively. When Poincare indexes SD1 and SD1/SD2 are considered, there are no systematic differences between the left and right fingertip signals (P > 0.5) however a systematic difference exists between the SD2 estimates (P=0.15). SD1 and SD1/SD2 estimates for the left and the right fingertips show high positive correlations of 1.00 and 0.99, respectively. However, a correlation of -0.30 exits for the left and the right fingertips when SD2 estimate is considered.

Ultrasound imaging with bolus delivered contrast agent for the detection of angiogenesis and blood flow irregularities.

Highly increased blood flow and vascularity after angiogenic gene therapy have raised concerns of shunting and hemangioma-like blood pool formation that might decrease effective perfusion and ruin the beneficial effects of the therapy. Contrast enhanced ultrasound is a promising noninvasive tool for studying skeletal muscle perfusion. The objectives of the present study were to test bolus and infusion administrations of ultrasound microbubble contrast media in imaging vascular growth in skeletal muscle and assess the functionality of vessels grown with angiogenic gene therapy. Contrast enhanced ultrasound was used to study changes in skeletal muscle perfusion in normal and gene-transduced rabbit hindlimbs 6 days after gene transfer. Adenoviral gene transfer of VEGF (10e(9)-10e(11) viral particles) or β-galactosidase control gene (10e(11) viral particles) was done under anesthesia and induced up to 16-fold increases in relative tissue perfusion. Contrast intensity versus time curves were plotted and analyzed for contrast kinetics. Bolus administration of the contrast media was highly feasible in analyzing skeletal muscle blood flow and its kinetics. Maximal signal intensity of the bolus signal reflected relative changes in both blood flow and volume equally to the infusion method. Flow irregularities were detected after angiogenic gene therapy. In conclusion, bolus delivery of ultrasound contrast agent is highly feasible for the relative analysis of both quantity and quality of blood flow after angiogenic gene therapy. The kinetics of blood flow can and should be studied more extensively in both preclinical and clinical trials of angiogenic gene therapy since there is increasing evidence of flow irregularities in angiogenic vessels.

The relative trending accuracy of noninvasive continuous hemoglobin monitoring during hemodialysis in critically ill patients.

The pulse CO-Oximeter (Radical-7; Masimo Corp., Irvine, CA) is a multi-wavelength spectrophotometric method for noninvasive continuous monitoring of hemoglobin (SpHb). Because evaluating the relative change in blood volume (ΔBV) is crucial to avoid hypovolemia and hypotension during hemodialysis, it would be of great clinical benefit if ΔBV could be estimated by measurement of SpHb during hemodialysis. The capability of the pulse CO-Oximeter to monitor ΔBV depends on the relative trending accuracy of SpHb. The purpose of the current study was to evaluate the relative trending accuracy of SpHb by the pulse CO-Oximeter using Crit-Line as a reference device. In 12 patients who received hemodialysis (total 22 sessions) in the intensive care unit, ΔBV was determined from SpHb. Relative changes in blood volume determined from SpHb were calculated according to the equation: ΔBV(SpHb)=[starting SpHb]/[current SpHb] - 1. The absolute values of SpHb and hematocrit measured by Crit-Line (CL-Hct) showed poor correlation. On the contrary, linear regression analysis showed good correlation between ΔBV(SpHb) and the relative change in blood volume measured by Crit-Line [ΔBV(CL-Hct)] (r=0.83; P≤0.001). Bland-Altman analysis also revealed good agreement between ΔBV(SpHb) and ΔBV(CL-Hct) (bias, -0.77%; precision, 3.41%). Polar plot analysis revealed good relative trending accuracy of SpHb with an angular bias of 4.1° and radial limits of agreement of 24.4° (upper) and -16.2° (lower). The results of the current study indicate that SpHb measurement with the pulse CO-Oximeter has good relative trending accuracy.