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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

WE-FG-206-05: New Arterial Spin Labeling Method for Simultaneous Estimation of Arterial Cerebral Blood Volume, Cerebral Blood Flow and Arterial Transit Time

Purpose: To demonstrate the feasibility of a novel Arterial Spin Labeling (ASL) method for simultaneously measuring cerebral blood flow (CBF), arterial transit time (ATT), and arterial cerebral blood volume (aCBV) without the use of a contrast agent. Methods: A series of multi-TI ASL images were acquired from one healthy subject on a 3T Siemens Skyra, with the following parameters: PCASL labeling with variable TI [300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000] ms, labeling bolus 1400 ms when TI allows, otherwise 100 ms less than TI, TR was minimized for each TI, two sinc shaped pre-saturation pulses were applied in the imaging plane immediately before 2D EPI acquisition. 64×64×24 voxels, 5 mm slice thickness, 1 mm gap, full brain coverage, 6 averages per TI, no crusher gradients, 11 ms TE, scan time of 4:56. The perfusion weighted time-series was created for each voxel and fit to a novel model. The model has two components: 1) the traditional model developed by Buxton et al., accounting for CBF and ATT, and 2) a box car function characterizing the width of the labeling bolus, with variable timing and height in proportion to the aCBV. All three parameters were fit using a nonlinear fitting routine that constrained all parameters to be positive. The main purpose of the high-temporal resolution TI sampling for the first second of data acquisition was to precisely estimate the blood volume component for better detection of arrival time and magnitude of signal. Results: Whole brain maps of CBF, ATT, and aCBV were produced, and all three parameters maps are consistent with similar maps described in the literature. Conclusion: Simultaneous mapping of CBF, ATT, and aCBV is feasible with a clinically tractable scan time (under 5 minutes).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

SU-E-J-241: Wavelet-Based Temporal Feature Extraction From DCE-MRI to Identify Sub-Volumes of Low Blood Volume in Head-And-Neck Cancer

Purpose: A previous study showed that large sub-volumes of tumor with low blood volume (BV) (poorly perfused) in head-and-neck (HN) cancers are significantly associated with local-regional failure (LRF) after chemoradiation therapy, and could be targeted with intensified radiation doses. This study aimed to develop an automated and scalable model to extract voxel-wise contrast-enhanced temporal features of dynamic contrastenhanced (DCE) MRI in HN cancers for predicting LRF. Methods: Our model development consists of training and testing stages. The training stage includes preprocessing of individual-voxel DCE curves from tumors for intensity normalization and temporal alignment, temporal feature extraction from the curves, feature selection, and training classifiers. For feature extraction, multiresolution Haar discrete wavelet transformation is applied to each DCE curve to capture temporal contrast-enhanced features. The wavelet coefficients as feature vectors are selected. Support vector machine classifiers are trained to classify tumor voxels having either low or high BV, for which a BV threshold of 7.6% is previously established and used as ground truth. The model is tested by a new dataset. The voxel-wise DCE curves for training and testing were from 14 and 8 patients, respectively. A posterior probability map of the low BV class was created to examine the tumor sub-volume classification. Voxel-wise classification accuracy was computed to evaluate performance of the model. Results: Average classification accuracies were 87.2% for training (10-fold crossvalidation) and 82.5% for testing. The lowest and highest accuracies (patient-wise) were 68.7% and 96.4%, respectively. Posterior probability maps of the low BV class showed the sub-volumes extracted by our model similar to ones defined by the BV maps with most misclassifications occurred near the sub-volume boundaries. Conclusion: This model could be valuable to support adaptive clinical trials with further validation. The framework could be extendable and scalable to extract temporal contrastenhanced features of DCE-MRI in other tumors. We would like to acknowledge NIH for funding support: UO1 CA183848.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Suggested reference values for regional blood volumes in children and adolescents

Estimates of regional blood volumes (BVs) in humans are needed in dosimetric models of radionuclides and radiopharmaceuticals that decay in the circulation to a significant extent. These values are also needed to refine models of tissue elemental composition in computational human phantoms of both patients and exposed members of the general public. The International Commission on Radiological Protection (ICRP) in its Publication 89 provides reference values for total blood content in the full series of their reference individuals, to include the male and female newborn, 1 year-old, 5 year-old, 10 year-old, 15 year-old, and adult. Furthermore, Publication 89 provides reference values for the percentage distribution of total blood volume in 27 different blood-filled organs and tissues of the reference adult male and adult female. However, no similar distribution values are provided for non-adults. The goal of the present paper is to present a volumetric scaling methodology to derive these values for the same organs and tissues at ages younger than the reference adult. Finally, literature data on organ-specific vascular growth in the brain, kidneys, and skeletal tissues are also considered.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

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

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

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-G-IeP1-12: Size Selective Arterial Cerebral Blood Volume Mapping Using Multiple Inversion Time Arterial Spin Labeling

Purpose: To demonstrate the feasibility of a novel method for size specific arterial cerebral blood volume (aCBV) mapping using pseudo-continuous arterial spin labeling (PCASL), with multiple TI. Methods: Multiple PCASL images were obtained from a subject with TI of [300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000] ms. Each TI pair was averaged six times. Two scans were performed: one without a flow crusher gradient and the other with a crusher gradient (10cm/s in three directions) to remove signals from large arteries. Scan times were 5min. without a crusher gradient and 5.5 min with a crusher gradient. Non-linear fitting algorithm finds the minimum mean squared solution of per-voxel based aCBV, cerebral blood flow, and arterial transit time, and fits the data into a hemodynamic model that represents superposition of blood volume and flow components within a single voxel. Results: aCBV maps with a crusher gradient represent signals from medium and small sized arteries, while those without a crusher gradient represent signals from all sized arteries, indicating that flow crusher gradients can be effectively employed to achieve size-specific aCBV mapping. Regardless of flow crusher, the CBF and ATT maps are very similar in appearance. Conclusion: Quantitative size selective blood volume mapping controlled by a flow crusher is feasible without additional information because the ASL quantification process doesn’t require an arterial input function measured from a large artery. The size specific blood volume mapping is not interfered by sSignals from large arteries do not interfere with size specific aCBV mapping in the applications of interest in for applications in which only medium or small arteries are of interest.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Does Preinterventional Flat-Panel Computer Tomography Pooled Blood Volume Mapping Predict Final Infarct Volume After Mechanical Thrombectomy in Acute Cerebral Artery Occlusion?

PurposeDecreased cerebral blood volume is known to be a predictor for final infarct volume in acute cerebral artery occlusion. To evaluate the predictability of final infarct volume in patients with acute occlusion of the middle cerebral artery (MCA) or the distal internal carotid artery (ICA) and successful endovascular recanalization, pooled blood volume (PBV) was measured using flat-panel detector computed tomography (FPD CT).Materials and MethodsTwenty patients with acute unilateral occlusion of the MCA or distal ACI without demarcated infarction, as proven by CT at admission, and successful Thrombolysis in cerebral infarction score (TICI 2b or 3) endovascular thrombectomy were included. Cerebral PBV maps were acquired from each patient immediately before endovascular thrombectomy. Twenty-four hours after recanalization, each patient underwent multislice CT to visualize final infarct volume. Extent of the areas of decreased PBV was compared with the final infarct volume proven by follow-up CT the next day.ResultsIn 15 of 20 patients, areas of distinct PBV decrease corresponded to final infarct volume. In 5 patients, areas of decreased PBV overestimated final extension of ischemia probably due to inappropriate timing of data acquisition and misery perfusion.ConclusionPBV mapping using FPD CT is a promising tool to predict areas of irrecoverable brain parenchyma in acute thromboembolic stroke. Further validation is necessary before routine use for decision making for interventional thrombectomy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Interrelationship between sex, age, blood volume and VO 2 max

Background Circulating blood volume (BV) and maximal oxygen uptake (VO 2 max) are physiological characteristics important for optimal human performance in aerospace and military operational environments. Addressing the interrelationships between BV, VO 2 max, sex, and age together is relevant to identifying those individuals with greatest risk of poor outcomes from hemorrhage, as well as assessing the levels of performance competence of individuals deployed in operational environments. In the present investigation, we report and compare for the first time BV and VO 2 max in a cohort of males and females together to test the hypothesis that BV and VO 2 max is lower in older people independent of sex. Methods To accomplish this, a ‘data mining’ effort of an historic database generated from NASA and U.S. Air Force experiments was conducted. BV, red cell volume, plasma volume, hematocrit, and VO 2 max were measured in 94 healthy individuals (28 females, 66 males) across an age range of 23 to 65 years to assess the interrelationship between sex, age, BV, and VO 2 max. Subjects were classified in age groups by < 40 years and ≥ 40 years; these groups identified females as pre‐ vs. post‐menopausal. Results Consistent with our hypothesis, comparisons revealed that males had higher (p < 0.01) BV, red cell volume, hematocrit, and VO 2 max than females when standardized for body size. Against expectations, BV was not different in older compared with younger males and females. VO 2 max was not different in older compared with younger females, while VO 2 max was lower in older males (p < 0.01). Conclusion We conclude that physiological mechanisms other than BV associated with aging appear to be responsible for a decline in VO 2 max of our older male subjects. Furthermore, factors other than menopause may also influence the control of BV in the female population. Our results provide evidence that aging may not compromise males or females in scenarios where BV can affect performance in aerospace and military environments. Support or Funding Information This research was supported in part by appointment of Ms. Koons to the Postgraduate Research Fellowship Program at the US Army Institute of Surgical Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and USAMRMC. Study funding was provided by a grant from the US Army Combat Casualty Care Research Program (D‐009‐2014‐USAISR). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Convertino, Victor↗
DOE OSTI2018

Quantification of intramyocardial blood volume with {sup 99m}Tc-RBC SPECT-CT imaging: A preclinical study

Background: Currently, there is no established non-invasive imaging approach to directly evaluate myocardial microcirculatory function in order to diagnose microvascular disease independent of co-existing epicardial disease. In this work, we developed a methodological framework for quantification of intramyocardial blood volume (IMBV) as a novel index of microcirculatory function with SPECT/CT imaging of {sup 99m}Tc-labeled red blood cells (RBCs). Methods: Dual-gated myocardial SPECT/CT equilibrium imaging of {sup 99m}Tc-RBCs was performed on twelve canines under resting conditions. Five correction schemes were studied: cardiac gating with no other corrections (CG), CG with attenuation correction (CG + AC), CG + AC with scatter correction (CG + AC + SC), dual cardiorespiratory gating with AC + SC (DG + AC + SC), and DG + AC + SC with partial volume correction (DG + AC + SC + PVC). Quantification of IMBV using each approach was evaluated in comparison to those obtained from all corrections. The in vivo SPECT estimates of IMBV values were validated against those obtained from ex vivo microCT imaging of the casted hearts. Results: The estimated IMBV with all corrections was 0.15 ± 0.03 for the end-diastolic phase and 0.11 ± 0.03 for the end-systolic phase. The cycle-dependent change in IMBV (ΔIMBV) with all corrections was 23.9 ± 8.6%. Schemes that applied no correction or partial correction resulted in significant over-estimation of IMBV and significant under-underestimation of ΔIMBV. Estimates of IMBV and ΔIMBV using all corrections were consistent with values reported in the literature using invasive techniques. In vivo SPECT estimates of IMBV strongly correlated (R{sup 2} ≥ 0.70) with ex vivo measures for the various correction schemes, while the fully corrected scheme yielded the smallest bias. Conclusions: Non-invasive quantification of IMBV is feasible using {sup 99m}Tc-RBCs SPECT/CT imaging, however, requires full compensation of physical degradation factors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Early MRI Blood Volume Changes in Constrictor Muscles Correlate With Postradiation Dysphagia

Predicting individual patient sensitivity to radiation therapy (RT) for tumor control or normal tissue toxicity is necessary to individualize treatment planning. In head and neck cancer, radiation doses are limited by many nearby critical structures, including structures involved in swallowing. Previous efforts showed that imaging parameters correlate with RT dose; here, we investigate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) blood volume (BV) changes in predicting dysphagia.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Low Cerebral Blood Volume Identifies Poor Outcome in Stent Retriever Thrombectomy

BackgroundMechanical thrombectomy (MT) is an efficient treatment of acute stroke caused by large-vessel occlusion. We evaluated the factors predicting poor clinical outcome (3-month modified Rankin Scale, mRS >2) although MT performed with modern stent retrievers.MethodsWe prospectively collected the clinical and imaging data of 105 consecutive anterior circulation stroke patients who underwent MT after multimodal CT imaging. Patients with occlusion of the internal carotid artery and/or middle cerebral artery up to the M2 segment were included. We recorded baseline clinical, procedural and imaging variables, technical outcome, 24-h imaging outcome and the clinical outcome. Differences between the groups were studied with appropriate statistical tests and binary logistic regression analysis.ResultsLow cerebral blood volume Alberta stroke program early CT score (CBV-ASPECTS) was associated with poor clinical outcome (median 7 vs. 9, p = 0.01). Lower collateral score (CS) significantly predicted poor outcome in regression modelling with CS = 0 increasing the odds of poor outcome 4.4-fold compared to CS = 3 (95% CI 1.27–15.5, p = 0.02). Lower CBV-ASPECTS significantly predicted poor clinical outcome among those with moderate or severe stroke (OR 0.82, 95% CI 0.68–1, p = 0.05) or poor collateral circulation (CS 0–1, OR 0.66, 95% CI 0.48–0.90, p = 0.009) but not among those with mild strokes or good collaterals.ConclusionsCBV-ASPECTS estimating infarct core is a significant predictor of poor clinical outcome among anterior circulation stroke patients treated with MT, especially in the setting of poor collateral circulation and/or moderate or severe stroke.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

SU-F-R-51: Radiomics in CT Perfusion Maps of Head and Neck Cancer

Purpose: The aim of this study was to test the predictive value of radiomics features of CT perfusion (CTP) for tumor control, based on a preselection of radiomics features in a robustness study. Methods: 11 patients with head and neck cancer (HNC) and 11 patients with lung cancer were included in the robustness study to preselect stable radiomics parameters. Data from 36 HNC patients treated with definitive radiochemotherapy (median follow-up 30 months) was used to build a predictive model based on these parameters. All patients underwent pre-treatment CTP. 315 texture parameters were computed for three perfusion maps: blood volume, blood flow and mean transit time. The variability of texture parameters was tested with respect to non-standardizable perfusion computation factors (noise level and artery contouring) using intraclass correlation coefficients (ICC). The parameter with the highest ICC in the correlated group of parameters (inter-parameter Spearman correlations) was tested for its predictive value. The final model to predict tumor control was built using multivariate Cox regression analysis with backward selection of the variables. For comparison, a predictive model based on tumor volume was created. Results: Ten parameters were found to be stable in both HNC and lung cancer regarding potentially non-standardizable factors after the correction for inter-parameter correlations. In the multivariate backward selection of the variables, blood flow entropy showed a highly significant impact on tumor control (p=0.03) with concordance index (CI) of 0.76. Blood flow entropy was significantly lower in the patient group with controlled tumors at 18 months (p<0.1). The new model showed a higher concordance index compared to the tumor volume model (CI=0.68). Conclusion: The preselection of variables in the robustness study allowed building a predictive radiomics-based model of tumor control in HNC despite a small patient cohort. This model was found to be superior to the volume-based model. The project was supported by the KFSP Tumor Oxygenation of the University of Zurich, by a grant of the Center for Clinical Research, University and University Hospital Zurich and by a research grant from Merck (Schweiz) AG.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Effects of haemodilution on the optical properties of blood during coagulation studied by optical coherence tomography

We report an investigation of the effects of blood dilution with hypertonic (7.5 %) and normal (0.9 %) saline on its optical properties during coagulation in vitro using optical coherence tomography. The light penetration depth and attenuation coefficient are obtained from the dependences of reflectance on the depth. Normal whole blood has served as the control group. The average coagulation time is equal to 420±16,418±16 and 358±14 s with blood volume replacement of 2 %, 11 %, and 20 % by 0.9 % normal saline, respectively. With 2 %, 11% and 20% blood volume replacement with 7.5 % hypertonic saline, the average coagulation time is 422±17,1160±45 and 1730±69 s, respectively. For normal whole blood, the average coagulation time amounts to 425±19 s. it is shown that dilution with normal saline has a procoagulant effect when it replaces 20 % of blood volume, and hypertonic saline has an anticoagulant effect if it replaces 11 % or more of blood volume. It is concluded that optical coherence tomography is a potential technique to quantify and monitor the liquid – gel transition during the coagulation process of blood diluted by normal and hypertonic saline. (biophotonics)

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Efficacy of perfusion CT in differentiating of pancreatic ductal adenocarcinoma from mass-forming chronic pancreatitis and characterization of isoattenuating pancreatic lesions

Purpose: Multidetector computed tomography (MDCT) is routinely used in the diagnosis of pancreatic ductal adenocarcinoma (PDAC), but it may be inadequate in some cases, especially mass-forming chronic pancreatitis (MFCP) and isoattenuating pancreatic lesions. Perfusion CT (pCT) may help resolve this problem. The aim of this study was to evaluate whether pCT could help differentiating PDAC from MFCP and in characterization of isoattenuating pancreatic lesions. Materials and methods: This prospective study included 89 cases of pancreatic lesions detected by MDCT and further analyzed with pCT. Sixty-one cases with final pathological diagnosis PDAC and 12 cases with MFCP were included from the study. Blood volume (BV), blood flow (BF), mean transit time (MTT), and permeability surface area product (PS) maps were obtained. Perfusion values obtained from the lesions and normal parenchyma were compared. Results: Compared with normal parenchyma, BV, BF, PS were lower and MTT was longer in PDAC and MFCP (p < 0.05). Compared with MFCP, BV, BF, PS were lower and MTT was longer in PDAC (p < 0.001). Compared with normal parenchyma, BV, BF, PS were lower and MTT was longer in isoattenuating lesions, (p < 0.001). Cutoff values of 7.60 mL/100 mL, 64.43 mL/100 mL/min, 28.08 mL/100 mL/min for BV, BF, PS, respectively, provided 100% sensitivity and specificity and 7.47 s for MTT provided 98.3% sensitivity, 80% specificity for distinguishing PDAC from MFCP. Conclusion: pCT is a useful technology that can be helpful in overcoming the limitations of routine MDCT in diagnosing PDAC and characterization of isoattenuating lesions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

SU-F-J-220: Micro-CT Based Quantification of Mouse Brain Vasculature: The Effects of Acquisition Technique and Contrast Material

Purpose: Cognitive impairment from radiation therapy to the brain may be linked to the loss of total blood volume in the brain. To account for brain injury, it is crucial to develop an understanding of blood volume loss as a result of radiation therapy. This study investigates µCT based quantification of mouse brain vasculature, focusing on the effect of acquisition technique and contrast material. Methods: Four mice were scanned on a µCT scanner (Siemens Inveon). The reconstructed voxel size was 18µm3 and all protocols were Hounsfield Unit (HU) calibrated. The mice were injected with 40mg of gold nanoparticles (MediLumine) or 100µl of Exitron 12000 (Miltenyi Biotec). Two acquisition techniques were also performed. A single kVp technique scanned the mouse once using an x-ray beam of 80kVp and segmentation was completed based on a threshold of HU values. The dual kVp technique scanned the mouse twice using 50kVp and 80kVp, this segmentation was based on the ratio of the HU value of the two kVps. After image reconstruction and segmentation, the brain blood volume was determined as a percentage of the total brain volume. Results: For the single kVp acquisition at 80kVp, the brain blood volume had an average of 3.5% for gold and 4.0% for Exitron 12000. Also at 80kVp, the contrast-noise ratio was significantly better for images acquired with the gold nanoparticles (2.0) than for those acquired with the Exitron 12000 (1.4). The dual kVp acquisition shows improved separation of skull from vasculature, but increased image noise. Conclusion: In summary, the effects of acquisition technique and contrast material for quantification of mouse brain vasculature showed that gold nanoparticles produced more consistent segmentation of brain vasculature than Exitron 12000. Also, dual kVp acquisition may improve the accuracy of brain vasculature quantification, although the effect of noise amplification warrants further study.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma

Purpose: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results: HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions: HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Quantifying tissue mechanical properties using photoplethysmography

Photoplethysmography (PPG) is a non-invasive optical method that can be used to detect blood volume changes in the microvascular bed of tissue. The PPG signal comprises two components; a pulsatile waveform (AC) attributed to changes in the interrogated blood volume with each heartbeat, and a slowly varying baseline (DC) combining low frequency fluctuations mainly due to respiration and sympathetic nervous system activity. In this report, we investigate the AC pulsatile waveform of the PPG pulse for ultimate use in extracting information regarding the biomechanical properties of tissue and vasculature. By analyzing the rise time of the pulse in the diastole period, we show that PPG is capable of measuring changes in the Young s Modulus of tissue mimicking phantoms with a resolution of 4 KPa in the range of 12 to 61 KPa. In addition, the shape of the pulse can potentially be used to diagnose vascular complications by differentiating upstream from downstream complications. A Windkessel model was used to model changes in the biomechanical properties of the circulation and to test the proposed concept. The modeling data confirmed the response seen in vitro and showed the same trends in the PPG rise and fall times with changes in compliance and vascular resistance.

Akl, Tony↗
DOE OSTI2014

MO-G-BRF-06: Radiotherapy and Prompt Oxygen Dynamics

Purpose: Adaptive radiotherapy requires a knowledge of the changing local tumor oxygen concentrations for times on the order of the treatment time, a time scale far shorter than cell death and proliferation. This knowledge will be needed to guide hypofractionated radiotherapy. Methods: A diffuse optical probe system was developed to spatially average over the whole interior of athymic Sprague Dawley nude mouse xenografts of human head and neck cancers. The blood volume and hemoglobin saturation was measured in real time. The quantities were measured with spectral fitting before and after 10 Gy of radiation is applied. An MRI BOLD scan is acquired before and after 10 Gy that measures regional changes in R2* which is inversely proportional to oxygen availability. Simulations were performed to fit the blood oxygen dynamics and infer changes in hypoxia within the tumor. Results: The optical probe measured nearly constant blood volume and a significant drop in hemoglobin saturation of about 30% after 10 Gy over the time scale of less than 30 minutes. The averaged R2* within the tumor volume increased by 15% after the 10 Gy dose, which is consistent with the optical results. The simulations and experiments support likely dynamic metabolic changes and/or fast vasoconstrictive signals are occurring that change the oxygen concentrations significantly, but not cell death or proliferation. Conclusion: Significant oxygen changes were observed to occur within 30 minutes, coinciding with the treatment time scale. This dynamic is very important for patient specific adaptive therapy. For hypofractionated therapy, the local instantaneous oxygen content is likely the most important variable to control. The invention of a bedside device for the purpose of measuring the instantaneous response to large radiation doses would be an important step to future improvements in outcome.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Tracking DO 2 with Compensatory Reserve during Whole Blood Resuscitation in Baboons

Background Hemorrhagic shock can be mitigated by timely and accurate resuscitation designed to restore adequate delivery of oxygen (DO 2 ) by increasing cardiac output (CO). However, standard care of using systolic blood pressure (SBP) as a guide for resuscitation has proven ineffective and can be associated with increased morbidity. We have developed a novel vital sign called the compensatory reserve (CRM) generated from analysis of arterial pulse waveform feature changes that has been validated in experimental and clinical models of hemorrhage. We tested the hypothesis that thresholds of DO 2 could be accurately defined by CRM while avoiding over resuscitation during whole blood resuscitation following a 25% hemorrhage in non‐human primates. Methods To accomplish this, adult male baboons (n=12) were exposed to a progressive controlled hemorrhage that resulted in an average (± SD) maximal reduction of 601 ± 18 ml of their estimated circulating blood volume of 1,262 ± 64 ml based on body weight. Values of DO 2 were calculated as the product of CO times O 2 carrying capacity of hemoglobin (i.e., Hb content × 1.34). Results Average (± SD) CRM increased from 6 ± 5 % at the end of hemorrhage to 70 ± 7 % at the end of resuscitation. DO 2 of 12.1, 10.3, and 7.0 ml O 2 ·kg −1 ·min −1 were calculated at 0% (baseline), 12.5% and 25% blood loss. By linear regression, CRM values of 6% (decompensation), 35%, and 68% corresponded to calculated DO 2 values of 6.0, 9.2, and 12.1 ml O 2 ·kg −1 ·min −1 during resuscitation. As such, return of CRM to baseline during resuscitation with only ~ 450 ml provided adequate DO 2 (12.5 ml O 2 ·kg −1 ·min −1 ) while total blood volume replacement (~600 ml) resulted in over resuscitation as indicated by an average increase in SBP (+17 mmHg) and CO (+0.1 L/min) over baseline values. Conclusion Consistent with our hypothesis, thresholds of DO 2 were associated with specific CRM values. A target resuscitation CRM value of 70% minimized the requirement for whole blood, while avoiding over resuscitation. Furthermore, CRM at 0% provided a noninvasive metric for determining critical DO 2 at approximately 5.4 ml O 2 ·kg −1 ·min −1 . Support or Funding Information This research was supported in part by appointment of Ms. Koons to the Postgraduate Research Fellowship Program at the US Army Institute of Surgical Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and USAMRMC. Study funding was provided by a grant from the US Army Combat Casualty Care Research Program (D‐009‐2014‐USAISR). Linearregression of the relationship between DO 2 and compensatory reserve during whole blood resuscitation in baboons. Data are expressed as mean ± SE. image Linearregression of the relationship between DO 2 and compensatory reserve during whole blood resuscitation in baboons. Data are expressed as mean ± SE. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Koons, Natalie Jane↗