Relative Blood Volume Changes Research Articles

Cerebral Blood Volume Alterations in the Perilesional Areas in the Rat Brain after Traumatic Brain Injury—Comparison with Behavioral Outcome

In the traumatic brain injury (TBI) the initial impact causes both primary injury, and launches secondary injury cascades. One consequence, and a factor that may contribute to these secondary changes and functional outcome, is altered hemodynamics. The relative cerebral blood volume (CBV) changes in rat brain after severe controlled cortical impact injury were characterized to assess their interrelations with motor function impairment. Magnetic resonance imaging (MRI) was performed 1, 2, 4 h, and 1, 2, 3, 4, 7, and 14 days after TBI to quantify CBV and water diffusion. Neuroscore test was conducted before, and 2, 7, and 14 days after the TBI. We found distinct temporal profile of CBV in the perilesional area, hippocampus, and in the primary lesion. In all regions, the first response was drop of CBV. Perifocal CBV was reduced for over 4 days thereafter gradually recovering. After the initial drop, the hippocampal CBV was increased for 2 weeks. Neuroscore demonstrated severely impaired motor functions 2 days after injury (33% decrease), which then slowly recovered in 2 weeks. This recovery parallelled the recovery of perifocal CBV. CBV MRI can detect cerebrovascular pathophysiology after TBI in the vulnerable perilesional area, which seems to potentially associate with time course of sensory-motor deficit.

Relative Plasma Volume Monitoring and Blood Pressure Control

Establishing dry weight in hemodialysis patients is an inexact science.1 Monitoring changes in blood pressure with volume removal is crude but can be effective in establishing dry weight. Unfortunately, probing for dry weight (eg, reduction of volume on dialysis sufficient to reduce blood pressure to <140/90 mm Hg) can lead to intradialytic hypotension, and this is more common in patients with large intradialytic weight gain. Often clinicians use medication-directed blood pressure control strategies in the hemodialysis patient.2 This paradoxically may interfere with the opportunity to achieve dry weight, because if the patient is on increased amounts of antihypertensive medication, more sizeable reductions in blood pressure with ultrafiltration may occur during dialysis.3 This would limit the opportunity for volume removal. As a consequence, the patient would then be chronically volume overloaded. If antihypertensive medication escalation results from inadequate achievement of goal blood pressure during dialysis, a vicious cycle would ensue. The net result is more risk of adverse events from medications and increased ventricular volume and pressure. Recurrent ventricular volume overload may be one of the most important factors leading to heart failure and increased risk of arrhythmia. Thus, …

Assessing the blood volume and heart rate responses during haemodialysis in fluid overloaded patients using support vector regression

This study aims to assess the blood volume and heart rate (HR) responses during haemodialysis in fluid overloaded patients by a nonparametric nonlinear regression approach based on a support vector machine (SVM). Relative blood volume (RBV) and electrocardiogram (ECG) was recorded from 23 haemodynamically stable renal failure patients during regular haemodialysis. Modelling was performed on 18 fluid overloaded patients (fluid removal of >2 L). SVM-based regression was used to obtain the models of RBV change with time as well as the percentage change in HR with respect to RBV. Mean squared error (MSE) and goodness of fit (R2) were used for comparison among different kernel functions. The design parameters were estimated using a grid search approach and the selected models were validated by a k-fold cross-validation technique. For the model of HR versus RBV change, a radial basis function (RBF) kernel (MSE = 17.37 and R2 = 0.932) gave the least MSE compared to linear (MSE = 25.97 and R2 = 0.898) and polynomial (MSE = 18.18 and R2= 0.929). The MSE was significantly lower for training data set when using RBF kernel compared to other kernels (p < 0.01). The RBF kernel also provided a slightly better fit of RBV change with time (MSE = 1.12 and R2 = 0.91) compared to a linear kernel (MSE = 1.46 and R2 = 0.88). The modelled HR response was characterized by an initial drop and a subsequent rise during progressive reduction in RBV, which may be interpreted as the reflex response to a transition from central hypervolaemia to hypovolaemia. These modelled curves can be used as references to a controller that can be designed to regulate the haemodynamic variables to ensure the stability of patients undergoing haemodialysis.

Influence of ventilation mode on neonatal cerebral blood flow and volume

Background Cerebral hemodynamics is supposed to be influenced by the different ventilation approach. Ventilation support can be classified as non-invasive (N-CPAP) or invasive (SIMV and HFV), the last known to induce endotrauma. Our aim was the non-invasive NIRS assessment of neonatal absolute cerebral blood flow (CBF) and relative cerebral blood volume changes (ΔCBV) during synchronized intermittent ventilation (SIMV), or high frequency ventilation (HFV) and nasal continuous positive airways pressure (CPAP). Methods An observational study in a tertiary referral NICU. CBF and ΔCBV changes were assessed in 41 preterm newborn infants with respiratory distress syndrome treated using mechanical ventilation or the CPAP device. Results Basal chromophore traces enabled ΔCBV (mL/100 g) changes to be calculated. CBF was calculated in mL/100 g/min from the saturation rise integral and rate of rise [O 2Hb-HHb]. Median ΔCBV was 0.07 (range 0.01–0.13) in SIMV group, 0.07 (0.01–0.19) in HFV group and 0.13 (0.10–1.28) in CPAP group. Median CBF was 14.44 (2.70–32.10), 9.20 (2.94–19.58) and 31.69 (13.59–34.93) respectively. A multiple regression model showed a significant correlation between ΔCBV or CBF and ventilation approach. Conclusion In the light of our results, we might speculate that, assuming that hemodynamic autoregulation is safe and arterial blood pressure is preserved, ventilation per se influences brain circulation.

Feasibility of Using Bevacizumab With Radiation Therapy and Temozolomide in Newly Diagnosed High-Grade Glioma

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m(2). Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m(2) for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely.

Central venous oxygen saturation and thoracic admittance during dialysis: New approaches to hemodynamic monitoring

Intradialytic hypotension (IDH) is one of the most important short-term complications to hemodialysis (HD). Inadequate cardiac filling due to a reduction in the central blood volume is believed to be a major etiological factor. The aim of this study was to evaluate whether these pathophysiologic events are reflected in the central venous oxygen saturation (ScO(2)) and thoracic admittance (TA) during dialysis. Twenty ambulatory HD patients, 11 hypotension prone (HP) and 9 hypotension resistant, with central vascular access, were monitored during 3 HD sessions each. ScO(2), TA, finger blood pressure (BP), and relative change in blood volume (DeltaBV) were measured and sampled continuously. The relative TA decrease and DeltaBV were both largest in the HP group (p<0.05 for both), whereas ScO(2) decreased only in HP patients (p<0.001). Baseline TA was lower in the HP group (p<0.01). Changes in ScO(2) and TA correlated much closer than did changes in ScO(2) and DeltaBV (r=0.43 and 0.18, respectively). Our results suggest that an intradialytic decrease in cardiac output, as reflected by a fall in ScO(2), is a common feature to HD patients prone to IDH. In patients using a central vascular access, ScO(2) and TA measurements may be more specific to the pathophysiologic events preceding IDH than DeltaBV-the current standard monitoring method.

Comparison of dynamic susceptibility contrast MRI with conventional MRI in evaluating tumor response following bevacizumab therapy in recurrent high-grade gliomas

2085 Background: Dynamic susceptibility contrast-enhanced MRI (DSC MRI) has emerged as an important adjunctive biomarker to assess the effectiveness of antiangiogenic therapies in the treatment of brain tumors. The purpose of our study is to compare changes in relative cerebral blood volume (rCBV) and vascular permeability (KTrans) with those of tumor size measurements (T1c), in predicting tumor therapeutic response in recurrent high-grade gliomas treated with bevacizumab, an anti-VEGF monoclonal antibody. Methods: 28 patients with recurrent high grade gliomas received therapy with bevacizumab at 10 mg/kg every two weeks for four doses in an 8 week cycle along with irinotecan at 125 mg/M2. All patients had baseline DSC MRI scans prior to the administration of bevacizumab and were followed clinically and radiographically with both conventional and DSC MRI. Tumor size was measured using 2D Macdonald criteria. Mixed model regression was used to compare the pre-treatment and post-treatment levels of each resp...

Non-invasive characterization of β-amyloid 1-40 vasoactivity by functional magnetic resonance imaging in mice

Neurovascular regulation, which is critical to the efficient functioning of the brain, is impaired in Alzheimer's disease and in transgenic mice overexpressing Aβ. Although senile plaques and neurofibrillary tangles represent neuropathological hallmarks of Alzheimer's disease, deposition of Aβ in cerebral blood vessels also likely plays a significant role in this debilitating and fatal disease. Further, soluble Aβ, which shows greater correlation with disease progression and severity than deposited plaques or tangles, displays strong vasoactive properties. The aim of this study was to develop a non-invasive model of cerebral vasoactivity that would ultimately be translatable to Alzheimer's disease as a marker for disease-modifying efficacy of novel small molecule and biologics drugs. Relative changes in cerebral blood volume following relevant doses of soluble Aβ 1-40 (0.01 or 0.1 mg/mouse), PBS, or the reverse peptide, Aβ 40-1 (0.01 or 0.1 mg/mouse), were monitored non-invasively by contrast-enhanced functional magnetic resonance imaging in anesthetized C57BL/6 mice. Experiments were performed on a 7T horizontal bore scanner using gradient echo echo-planar imaging. As expected, PBS and Aβ 40-1 did not induce any significant change in vascular response. In contrast, Aβ 1-40 significantly decreased CBV in a quantifiable, dose-related and region-specific manner. These data demonstrate for the first time the feasibility of characterizing pathogenic Aβ 1-40-induced vascular dysfunction in vivo using a non-invasive approach. Further, this technique can be readily applied to preclinical screening in a longitudinal manner for novel drugs or antibodies targeting disease modification.

Low-Grade Gliomas: Do Changes in rCBV Measurements at Longitudinal Perfusion-weighted MR Imaging Predict Malignant Transformation?

To prospectively perform longitudinal magnetic resonance (MR) perfusion imaging of conservatively treated low-grade gliomas to determine whether relative cerebral blood volume (rCBV) changes precede malignant transformation as defined by conventional MR imaging and clinical criteria. All patients gave written informed consent for this institutional ethics committee-approved study. Thirteen patients (seven men, six women; age range, 29-69 years) with biopsy-proved low-grade glioma treated only with antiepileptic drugs were examined longitudinally with susceptibility-weighted perfusion, T2-weighted, fluid-attenuated inversion recovery, and high-dose contrast material-enhanced T1-weighted MR imaging at 6-month intervals to date or until malignant transformation was diagnosed. Student t tests were used to determine differences in rCBV values between "transformers" and "nontransformers" at defined time points throughout study follow-up. Seven patients showed progression to high-grade tumors between 6 and 36 months (mean, 22.3 months), and disease in six patients remained stable over a period of 12-36 months (mean, 23 months). Transformers had a slightly (but not statistically significantly) higher group mean rCBV than nontransformers at the point of study entry (1.93 vs 1.31). In nontransformers, the rCBV remained relatively stable and increased to only 1.52 over a mean follow-up of 23 months. In contrast, transformers showed a continuous increase in rCBV up to the point of transformation, when contrast enhancement became apparent on T1-weighted images. The group mean rCBV was 5.36 at transformation but also showed a significant increase from the initial study at 12 months (3.14, P = .022) and at 6 months (3.65, P = .049) before transformation. Rates of rCBV change between two successive time points were also significantly higher in transformers than in nontransformers. In transforming low-grade glioma, susceptibility-weighted MR perfusion imaging can demonstrate significant increases in rCBV up to 12 months before contrast enhancement is apparent on T1-weighted MR images.

Effect of Hemolysis and Free Hemoglobin on Optical Hematocrit Measurements in the Extracorporeal Circulation

Clinically significant hemolysis is a rare but serious problem in dialysis. Because hemolysis affects red blood cell count and optical density of plasma it has been speculated whether techniques used for online blood volume monitoring would be useful to detect hemolysis. In this study the influence of free hemoglobin on hematocrit and relative blood volume changes measured by optical means (CritLine, HemaMetrics, Kaysville, UT) were examined using an in vitro model with bovine blood. Free hemoglobin solutions were added in steps to circulating whole blood at baseline hematocrits covering a range from 30% to 60% and at blood flows of approximately 200 and 400 ml/min. The free hemoglobin concentration reached was in the range of 2 to 3 g/dl. The presence of free hemoglobin led to a relative increase in hematocrit in the range of 0.3% per 0.1 g of free hemoglobin per dl (+3% dl/g). As an increase in hematocrit is interpreted as a decrease in blood volume, this change referred to an apparent decrease in relative blood volume in the same order of magnitude (-3% dl/g). Effects were more pronounced at low baseline hematocrit. Thus, although optical hematocrit readings are affected by the presence of free hemoglobin the changes at levels associated with clinical symptoms appear to be too small to be accurately detected in the in vivo situation where the hematocrit and the resulting optical signal is affected by various physiological processes and therefore much noisier.

VASO‐based calculations of CBV change: Accounting for the dynamic CSF volume

The goal of the vascular space occupancy (VASO) imaging technique is to use selective nulling of the blood signal to infer relative changes in cerebral blood volume (CBV). In accordance with recent work, we show that changes in the local CSF fraction (x(c)) with activation can significantly impact the VASO signal, thereby limiting our ability to infer DeltaCBV from DeltaVASO alone. Here we calculate CBV change using a VASO-based method which ACcounts for the Dynamic Cerebrospinal (ACDC) fluid fraction. By combining data from two separate VASO acquisitions that eliminate either the blood signal (VASO(b)) or the CSF signal (VASO(c)), a nonlinear least-squares optimization may then be used to simultaneously solve for the relative changes in CBV and CSF with activation. The method is applied across the whole brain during a breath-holding task, offering insight into the relationship between changes in CBV and x(c) associated with global vasodilatation. Calculations of mean changes in CBV in different volumes of interest obtained from the proposed method compare much better with previous (gold-standard) PET data than traditional VASO methods that do not account for a nonzero Deltax(c) with activation. This confirms the necessity of incorporating the dynamic CSF volume into VASO-based calculations of DeltaCBV.

Relative blood volume measurements during hemodialysis: Comparisons between three noninvasive devices

The monitoring of relative blood volume changes (DeltaRBV) has been advocated for the prevention of hemodialysis (HD) hypotension. Stand-alone devices (Crit-Line) or devices incorporated into the HD apparatus (blood volume monitor [BVM], Hemoscan) are widely used for this purpose. Comparisons between devices are scarce. The aim of this study was, first, to compare DeltaRBV results from these 3 devices with DeltaRBV calculated from changes in laboratory-derived hemoglobin (DeltaRBV-lab-Hb) and, second, to compare DeltaRBV results between the different devices. Fourteen patients received 2 HD treatments in a randomized order: one with the Hemoscan and Crit-Line combination and one with the BVM and Crit-Line combination. DeltaRBV-lab-Hb was measured at 2 and 4 hr into the HD session. Bland-Altman analyses showed that DeltaRBV results from the 3 devices differed systematically from DeltaRBV-lab-Hb, i.e., the difference between the 3 devices and DeltaRBV-lab-Hb varied significantly (p<0.05) with the magnitude of the measurement. The interdevice comparison showed considerable differences in DeltaRBV results. At the end of the treatment, a significant difference (p<0.05) between DeltaRBV measured by the Hemoscan and Crit-Line device (-9.8+/-2.7% and -11.5+/-4%, respectively) was found. In most patients, a systematic difference between Crit-Line and Hemoscan and between Crit-Line and BVM was observed. Relative blood volume change measurements by Crit-Line, Hemoscan, and BVM yield results that differ systematically from the results obtained from laboratory-derived Hb changes. Furthermore, there are substantial differences in DeltaRBV results between the 3 DeltaRBV devices.

Pulse Oximetry: Basic Principles and Applications in Aerospace Medicine

Pulse oximeters are reliable, objective, and noninvasive monitors that have broad application in aerospace medicine. New technology enables pulse oximeters to perform well in adverse environments and measure additional parameters. Small, battery-powered devices can be used to monitor oxyhemoglobin saturation while in flight. Pulse oximeters use spectrophotometry to measure the ratio of oxyhemoglobin (Hbo2) to reduced hemoglobin (Hb) in arterial blood. This value is displayed as oxyhemoglobin saturation (Spo2). A plethysmographic waveform that resembles arterial waveform is also frequently displayed and may indicate relative changes in perfusion and blood volume. Loss and subsequent reappearance of this waveform during occlusion with a cuff has been used to measure systolic blood pressure during helicopter flight. Accurate determination of oxygen saturation requires a high quality arterial signal and is limited by errors resulting from calibration, motion and vibration, and dyshemoglobinemias. Vasoconstriction may result in decreased pulse amplitude and also impair accurate measurement. Conventional fingertip probes may interfere with the performance of required duties, while helmets and other restrictive clothing can impede the use of sensors on the forehead or ear. Recently introduced devices answer some of these limitations and enable measurement of additional parameters. For example, new probe designs permit more freedom of movement and include a contactless camera and a sensor that fits around a finger like an ordinary ring. This article explains the theory of operation and limitations of pulse oximetry, offers an update on new technology, and discusses applications of this technology in aerospace medicine.

Differential Effects of Antipsychotic and Glutamatergic Agents on the phMRI Response to Phencyclidine

Acute administration of NMDA receptor (NMDAR) antagonists such as phencyclidine (PCP) or ketamine induces symptoms that closely resemble those of schizophrenia in humans, a finding that has led to the hypothesis that a decreased NMDAR function may be a predisposing or even causative factor in schizophrenia. However, the precise neuropharmacological mechanisms underlying these effects remain to be fully elucidated. Here, we applied pharmacological MRI (phMRI) to examine the brain circuitry underlying the psychotomimetic action of PCP in the anesthetized rat, and investigated how these functional changes are modulated by drugs that possess distinct pharmacological mechanisms. Acute administration of PCP (0.5 mg/kg i.v.) produced robust and sustained positive relative cerebral blood volume (rCBV) changes in discrete cortico-limbo-thalamic regions. Pretreatment with the selective D2 dopamine antagonist raclopride (0.3 mg/kg i.p.) did not significantly affect the rCBV response to PCP, while the atypical antipsychotic clozapine (5 mg/kg i.p.) produced region-dependent effects, with complete suppression of the rCBV response in the thalamus, and weaker attenuation of the response in cortical and hippocampal structures. The response to PCP was strongly suppressed in all regions by pretreatment with two drugs that can inhibit aberrant glutamatergic activity: the anticonvulsant lamotrigine (10 mg/kg i.p.) and the mGluR2/3 agonist LY354740 (10 mg/kg i.p.). Taken together, our findings corroborate the pivotal role of dysfunctional glutamatergic neurotransmission in the functional response elicited by PCP, while the lack of effect of raclopride argues against a primary role of dopamine D2 receptor activation in this process. Finally, the thalamic effect of clozapine could be key to elucidating the functional basis of its pharmacological action.

Resting energy expenditure and thermal balance during isothermic and thermoneutral haemodialysis heat production does not explain increased body temperature during haemodialysis

During routine haemodialysis (HD) body temperature increases, which contributes to haemodynamic instability. The relative roles of increased heat production and/or incomplete heat transfer are not fully elucidated. Concomitant measurement of heat production and heat transfer may help to assess the factors determining thermal balance during HD. Thirteen stable non-diabetic maintenance HD patients were investigated during two HD procedures (isothermic, dT = 0, no change of body temperature; thermoneutral, dE = 0, no energy transfer between blood and dialysate), using a blood temperature monitor (BTM) in active mode. Energy transfer, blood and dialysate temperature, and relative blood volume change (dBV) were continuously recorded, and resting energy expenditure (REE; Deltatrac Datex) was measured repeatedly during each procedure. Fourteen healthy persons served as controls for REE comparison. In isothermic HD, median energy removal was 218 kJ/4 h HD (= heat flow -15.1 W). This cooling correlated with dBV induced by ultrafiltration (rho = 0.731, P < 0.01). There was no difference in dBV between isothermic (7.7%) and thermoneutral (8.1%) HD. Predialysis REE was 82.8 W/1.73 m(2), not different from controls. No variation in REE during HD was observed, except a small and transient increase after a light meal (5 and 4%). In the time course of REE, no difference between the procedures was found. Our findings suggest that stable maintenance HD patients have REE not different from healthy controls, that HD procedure per se does not significantly increase REE and that neither isothermic nor thermoneutral regimen has any influence on metabolic rate. Therefore, body temperature elevation during routine HD may rather be due to decreased heat removal. With the use of BTM in active mode, body temperature can be kept stable (isothermic HD), which requires active cooling. This negative energy transfer is proportional to decrease in blood volume induced by ultrafiltration.

Influence of Ultrafiltration Volume on Blood Volume Changes During Hemodialysis as Observed in Day-of-the-Week Analysis of Hemodialysis Sessions

Monitoring of relative blood volume changes (DeltaRBV) has been propagated for the prevention of hemodialysis hypotension. Although the influence of ultrafiltration volume on DeltaRBV is well-known, there is no mention in the literature that DeltaRBV results should be interpreted differently for the first, second, or third hemodialysis session of the week. To elucidate whether DeltaRBV and its derivative, DeltaRBV normalized for ultrafiltration volume (DeltaRBV/ultrafiltration ratio), vary systematically over the week, we separately analyzed these parameters for the first, second, and third hemodialysis session of the week in 13 chronic hemodialysis patients over a 17-week period. As expected, mean (+/-SD) ultrafiltration volume was significantly (p < 0.001) higher during the first session than during the second and third hemodialysis sessions (3163 +/- 615, 2622 +/- 674 and 2607 +/- 638 ml, respectively). DeltaRBV was significantly (p < 0.01) more negative at the first session than at the second and third hemodialysis sessions (-10.1 +/- 2.7, -9.3 +/- 3.0 and -9.3 +/- 3.1%, respectively). The DeltaRBV/ultrafiltration ratio was significantly (p < 0.01) less negative at the first session than at the second and third hemodialysis sessions (-3.2 +/- 0.6, -3.5 +/- 0.8 and -3.6 +/- 0.6%/l, respectively). In conclusion, DeltaRBV and the DeltaRBV/ultrafiltration ratio differ systematically between the first and other hemodialysis sessions in patients on a thrice-weekly hemodialysis schedule, most likely as a result of different ultrafiltration volumes.

Comparing cerebral blood volume and vascular permeability measurements with tumor volume measurements following anti-angiogenesis therapy in recurrent gliomas

2030 Background: Dynamic susceptibility contrast-enhanced MRI (DSC MRI) is emerging as an important adjunctive biomarker to assess the effectiveness of anti-angiogenic therapies in the treatment of brain tumors. The purpose of our study is to compare changes in relative cerebral blood volume (rCBV) and in perfusion-permeability index (KTrans) with those of tumor volume measurements (T1c, T2/Flair) in predicting tumor therapeutic response in recurrent high-grade gliomas treated with bevacizumab, an anti-VEGF monoclonal antibody. Methods: 11 patients were treated with one to four cycles of bevacizumab and CPT-11. Their histological diagnoses were: glioblastoma multiforme (n=7), anaplastic astrocytoma (n=2), anaplastic oligodendroglioma (n=1), and diffuse pontine glioma (n=1). All patients had baseline DSC MRI scans prior to the administration of bevacizumab and were followed clinically and radiographically with both conventional and DSC MRI. Mixed model regression was used to compare the pre-treatment and post-treatment levels of each response measure. Results: There were statistically significant reductions in both actual rCBV measurements and T1c enhancement following treatment with bevacizumab and CPT-11. The pretreatment rCBV and T1c rates of change (as determined per 100 days) correlated significantly with time (p values are 0.0229 and 0.0014, respectively), while only the post treatment rCBV demonstrated significant rate of change (p value = 0.0001), suggesting that rCBV may reflect the effects of bevacizumab better than tumor volume. However, when the changes in rate from pre- to post-treatment status were considered, both rCBV and T1c demonstrated significance (p= 0.0001, 0.0157, respectively). There was a trend towards females having higher mean levels of KTrans than males at the same time point relative to treatment onset, but the result was not statistically significant (p=0.072). Conclusions: rCBV as measured from DSC MRI can be used as a surrogate biomarker to determine therapeutic response to bevacizumab. This may influence the neurosurgical risk/benefit equation as well as alter the aggressiveness of the post-operative adjuvant therapy in patients with recurrent gliomas. No significant financial relationships to disclose.

Relative Blood Volume Changes Underestimate Total Blood Volume Changes during Hemodialysis

Measurements of relative blood volume changes (DeltaRBV) during hemodialysis (HD) are based on hemoconcentration and assume uniform mixing of erythrocytes and plasma throughout the circulation. However, whole-body hematocrit (Ht) is lower than systemic Ht. During HD, a change in the ratio between whole-body to systemic Ht (F cell ratio) is likely to occur as a result of a net shift of low Ht blood from the microcirculation to the macrocirculation. Hence, DeltaRBV may differ significantly from total blood volume changes (DeltaTBV). Therefore, this study compared DeltaRBV and DeltaTBV during HD. Plasma and erythrocyte volumes were measured using (125)I- and (123)I-radioiodinated albumin and (51)Cr-labeled erythrocytes, respectively. After validation of the standardized method in two patients on a nondialysis day, seven patients completed the protocol during HD. (125)I-albumin and (51)Cr-labeled erythrocytes were administered 20 min before the start of HD. (123)I-albumin was administered at 160 min into the HD session to quantify and correct for (125)I-albumin leakage. DeltaRBV was measured continuously throughout HD. The F cell ratio was derived from whole-body and systemic Ht. Total ultrafiltration volume was 2450 +/- 770 ml. TBV declined from 5905 +/- 824 to 4877 +/- 722 ml during HD. Thus, TBV declined 17.3 +/- 4.4%, whereas the RBV decline was only 8.2 +/- 3.7% (P = 0.001). The F cell ratio increased from 0.896 +/- 0.036 to 0.993 +/- 0.049 during HD (P = 0.002). DeltaRBV significantly underestimates DeltaTBV during HD. The rise in F cell ratio strongly suggests that during HD, blood translocates from the microcirculation to the macrocirculation, probably as a cardiovascular compensatory mechanism in response to hypovolemia.

RELATIVE BLOOD VOLUME BASED BIOFEEDBACK DURING HAEMODIALYSIS

Intra-dialytic hypotension is the most frequently occurring complication during haemodialysis and can lead to serious complications. Devices that continuously and non-invasively monitor relative blood volume (RBV) changes during HD are being advocated as a tool to maintain an adequate volume of the intravascular compartment in order to avoid dialysis hypotension. Nowadays, most manufacturers have incorporated a RBV monitor in their dialysis apparatus and two manufacturers have designed biofeedback devices that control intra-dialytic RBV changes. The goal of RBV based biofeedback systems is to prevent a severe or abrupt decrease in blood volume in order to prevent the development of dialysis hypotension. Biofeedback technologies can diminish the severity and/or frequency of dialysis hypotension. At present, however, a completely symptom-free HD is not a reality. The major reasons for this are patient characteristics such as cardiovascular co-morbidity and high UF rates and a lack of understanding of the relation between RBV changes and blood pressure/cardiovascular stability.

Treatment of post-dialytic orthostatic hypotension with an inflatable abdominal band in hemodialysis patients

The purpose of this study was to ascertain whether abdominal compression with an inflatable abdominal band, a device we developed, improved post-dialytic orthostatic hypotension (OH) in hemodialysis (HD) patients. Twenty-five chronic HD patients with intractable post-dialytic OH were recruited. Post-HD changes in systolic blood pressure (DeltaSBP) in the supine and standing positions were compared in the patients, measured with or without the use of the band. The study showed DeltaSBP after HD without the band was significantly greater than that measured before HD (-36.1+/-18.2 vs -13.1+/-16.8 mm Hg; P<0.0001). DeltaSBP after HD with the band was reduced significantly in comparison to DeltaSBP after HD without the band (-19.4+/-21.2 vs -36.1+/-18.2 mm Hg; P<0.002). Use of the band did not cause an elevation in SBP in the supine position (149.0+/-29.6 vs 155.4+/-25.7 mm Hg); however, it did increase SBP upon standing (129.6+/-27.3 vs 117.2+/-22.6 mm Hg; P<0.05). Eight patients in whom an increase in SBP of 25 mm Hg or more was achieved with the band were classified as responders. Ejection fraction was significantly higher (76.4+/-11.1 vs 61.9+/-13.6%; P<0.02) and atrial natriuretic peptide concentration significantly lower (27.9+/-22.0 vs 68.9+/-47.5 pg/ml; P<0.02) in responders than in non-responders. We conclude that the abdominal band was effective for overcoming post-dialytic OH, without elevating supine SBP in some patients.