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Autofluorescence of blood has been explored as a label free approach for detection of cell types, as well as for diagnosis and detection of infection, cancer, and other diseases. Although blood autofluorescence is used to indicate the presence of several physiological abnormalities with high sensitivity, it often lacks disease specificity due to use of a limited number of fluorophores in the detection of several abnormal conditions. In addition, the measurement of autofluorescence is sensitive to the type of sample, sample preparation, and spectroscopy method used for the measurement. Therefore, while current blood autofluorescence detection approaches may not be suitable for primary clinical diagnosis, it certainly has tremendous potential in developing methods for large scale screening that can identify high risk groups for further diagnosis using highly specific diagnostic tests. This review discusses the source of blood autofluorescence, the role of spectroscopy methods, and various applications that have used autofluorescence of blood, to explore the potential of blood autofluorescence in biomedical research and clinical applications., (© 2021 Wiley Periodicals LLC.)

Whole slide imaging (WSI) has moved the traditional manual slide inspection process to the era of digital pathology. A typical WSI system translates the sample to different positions and captures images using a high numerical aperture (NA) objective lens. Performing oil-immersion microscopy is a major obstacle for WSI as it requires careful liquid handling during the scanning process. Switching between dry objective and oil-immersion lens is often impossible as it disrupts the acquisition process. For a high-NA objective lens, the sub-micron depth of field also poses a challenge to acquiring in-focus images of samples with uneven topography. Additionally, it implies a small field of view for each tile, thus limiting the system throughput and resulting in a long acquisition time. Here we report a deep learning-enabled WSI platform, termed DeepWSI, to substantially improve the system performance and imaging throughput. With this platform, we show that images captured with a regular dry objective lens can be transformed into images comparable to that of a 1.4-NA oil immersion lens. Blurred images with defocus distance from -5 µm to +5 µm can be virtually refocused to the in-focus plane post measurement. We demonstrate an equivalent data throughput of >2 gigapixels per second, the highest among existing WSI systems. Using the same deep neural network, we also report a high-resolution virtual staining strategy and demonstrate it for Fourier ptychographic WSI. The DeepWSI platform may provide a turnkey solution for developing high-performance diagnostic tools for digital pathology.

Unintentional exposure to nitrite- or nitrate-containing toxic salts is a recognized cause of acquired methemoglobinemia (MetHb). This systemic alteration of the blood can be fatal if not recognized and treated promptly. The intentional ingestion of sodium nitrite (NaNO 2 ) or sodium nitrate (NaNO 3 ), causing MetHb, is an uncommon and recently identified method of suicide, with the first reported case in the literature occurring in New Zealand in 2010. In this case series we present 28 cases of sudden death of individuals with evidence of MetHb and/or toxic salt ingestion, occurring in the Province of Ontario, Canada, between the years 1980 and 2020, inclusive. Of the 28 deaths in our case series, 25 showed evidence of intentional ingestion of sodium nitrite or sodium nitrate salts. Our year-over-year data demonstrated this is an increasingly used method of suicide in our provincial population, with the majority of cases occurring in the final two years of our study. Postmortem detection of MetHb is typically established via screening techniques such as scene evidence suggesting fatal consumption of a toxic salt in addition to the characteristic grey-purple lividity observed upon the body. The diagnosis can be established via postmortem blood testing demonstrating elevated methemoglobin saturation. Additionally, we have confirmed that postmortem MRI in cases of MetHb demonstrates a T1-bright (hyperintense) signal of the blood; both within intracardiac blood on chest MRIs and postmortem blood samples in tubes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Automated image-based assessment of blood films has tremendous potential to support clinical haematology within overstretched healthcare systems. To achieve this, efficient and reliable digital capture of the rich diagnostic information contained within a blood film is a critical first step. However, this is often challenging, and in many cases entirely unfeasible, with the microscopes typically used in haematology due to the fundamental trade-off between magnification and spatial resolution. To address this, we investigated three state-of-the-art approaches to microscopic imaging of blood films which leverage recent advances in optical and computational imaging and analysis to increase the information capture capacity of the optical microscope: optical mesoscopy, which uses a giant microscope objective (Mesolens) to enable high-resolution imaging at low magnification; Fourier ptychographic microscopy, a computational imaging method which relies on oblique illumination with a series of LEDs to capture high-resolution information; and deep neural networks which can be trained to increase the quality of low magnification, low resolution images. We compare and contrast the performance of these techniques for blood film imaging for the exemplar case of Giemsa-stained peripheral blood smears. Using computational image analysis and shape-based object classification, we demonstrate their use for automated analysis of red blood cell morphology and visualization and detection of small blood-borne parasites such as the malarial parasite Plasmodium falciparum. Our results demonstrate that these new methods greatly increase the information capturing capacity of the light microscope, with transformative potential for haematology and more generally across digital pathology. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland., (© 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.)

Recently, there has been a renewed interest in low-field MRI. Contrast agents (CA) in MRI have magnetic behavior dependent on magnetic field strength. Therefore, the optimal contrast agent for low-field MRI might be different from what is used at higher fields. Ultra-small superparamagnetic iron-oxides (USPIOs), commonly used as negative CA, might also be used for generating positive contrast in low-field MRI. The purpose of this study was to determine whether an USPIO or a gadolinium based contrast agent is more appropriate at low field strengths. Relaxivity values of ferumoxytol (USPIO) and gadoterate (gadolinium based) were used in this research to simulate normalized signal intensity (SI) curves within a concentration range of 0-15 mM. Simulations were experimentally validated on a 0.25T MRI scanner. Simulations and experiments were performed using spin echo (SE), spoiled gradient echo (SGE), and balanced steady-state free precession (bSSFP) sequences. Maximum achievable SIs were assessed for both CAs in a range of concentrations on all sequences. Simulations at 0.25T showed a peak in SIs at low concentrations ferumoxytol versus a wide top at higher concentrations for gadoterate in SE and SGE. Experiments agreed well with the simulations in SE and SGE, but less in the bSSFP sequence due to overestimated relaxivities in simulations. At low magnetic field strengths, ferumoxytol generates similar signal enhancement at lower concentrations than gadoterate., Competing Interests: The authors have declared that no competing interests exist.

New processing techniques for manipulating blood and its components at a microfluidic scale are currently implemented. As for extracorporeal circulation, the in-line evaluation and monitoring of blood properties during these microfluidic techniques is a challenging task. Here, we show that the blood hematocrit can be measured non-invasively in a sub-millimeter medical tube using the non-Newtonian behavior of blood velocity profile. This hematocrit measurement is demonstrated on human blood with a simple Doppler ultrasound system. Results show a mean measurement error of 4.6 ± 1.3%Hct for hematocrit up to 52% and for 5 s-long ultrasonic signals. The simplicity and the measurement scale of the approach make it highly valuable for measuring hematocrit in new blood separation techniques. The approach may have an impact on in-vitro blood processing in general.

We introduce a proof of concept for multimode random laser (RL) emission with fresh whole blood (WB) as the active medium. The experimental principle is adapted from RL emission using rhodamine 6G (R6G). We achieved conditions for fresh WB to fluoresce with stochastic amplification of stimulated emission of radiation. The random conditions are placed with S i O 2 particles, suspended in isotonic solvent. The results we report are for: (1) R6G-RL, with 2 nm bandwidth centered at 567 nm, and (2) RL emission for WB at 969 nm and 437 nm, of sub-3 nm bandwidth. For validation purposes, we show that the pumping energy threshold for RL emission from blood is consistent with R6G-RL.

Recently developed dark-blood techniques such as Flow-Independent Dark-blood DeLayed Enhancement (FIDDLE) allow simultaneous visualization of tissue contrast-enhancement and blood-pool suppression. Critical to FIDDLE is the magnetization preparation, which accentuates differences between myocardium and blood-pool. Here, we compared magnetization transfer (MT)-preparation and T2-preparation for use with FIDDLE. Variants of FIDDLE were developed with MT- or T2-preparation modules and tested in 35 patients (11 at 1.5 T, 24 at 3 T). Images were acquired with each FIDDLE variant in an interleaved fashion 10 minutes after gadolinium administration with otherwise identical acquisition parameters. Images were visually and quantitatively assessed for artifacts and differences in right ventricle to left ventricle (RV-to-LV) blood-pool suppression. Bright artifacts, reflecting incomplete blood-pool suppression, were frequently observed in the left atrium with T2-preparation FIDDLE at 1.5 and 3 T (82% and up to 100% of patients, respectively). MT-preparation FIDDLE resulted in fewer patients with artifacts (0% at 1.5 T, 22% at 3 T; P < .01). Left atrial blood-pool signal was significantly more homogeneous with MT-preparation than with T2-preparation at 1.5 and 3 T (P < .001 for all comparisons). Visibly different RV-to-LV blood-pool suppression was observed with T2-preparation in 36% of patients at 1.5 T and up to 94% at 3 T. In these patients, RV blood-pool signal was elevated, reducing the conspicuity of the myocardial-RV blood-pool border. Conversely, there were no visible differences in RV-to-LV blood-pool suppression with MT-preparation. Quantitative assessment of differences in blood-pool suppression and blood-pool artifacts was consistent with visual analyses. We conclude that for dark blood-blood delayed-enhancement imaging of the heart, MT-preparation results in fewer bright blood-pool artifacts and more uniform blood-pool suppression than T2-preparation., (© 2020 John Wiley & Sons, Ltd.)

The classification of leukocytes in peripheral blood images is an important milestone to be achieved because it can greatly assist pathologists to diagnose diseases such as leukemia, anemia, and other blood disorders. To a certain extent, a good segmentation method for identifying leukocytes from their background is the first step to the efficient functioning of the leukocytes classification system. However, the morphological structure of leukocytes, poor contrast, and the variations in their shape and size lead to the degradation of the segmentation accuracy. In this paper, we propose a new leukocyte segmentation framework that first locates and then segments leukocytes from peripheral blood images. Here, the locations of the leukocytes are first identified using a novel edge strength cue (ESc), and later, the Grabcut model is deployed to obtain the segmentation of the leukocytes. The novelty lies in the way the location of the leukocytes is detected, and this improves the leukocyte segmentation accuracy. The experimental evaluation is performed on ALL-IDB1, Cellavision, and LISC datasets for leukocyte segmentation based on the detection of the ESc location. Experimental results are evaluated using precision, recall, and F-score measures. The proposed method outperforms the state-of-the-art techniques. Additionally, the computation time of the proposed method is analyzed and presented in the study. Graphical Abstract Leukocytes Location Detection and Segmentation.

Background and Aim: Detecting blood content in the gastrointestinal tract is one of the crucial applications of capsule endoscopy (CE). The suspected blood indicator (SBI) is a conventional tool used to automatically tag images depicting possible bleeding in the reading system. We aim to develop a deep learning-based system to detect blood content in images and compare its performance with that of the SBI., Methods: We trained a deep convolutional neural network (CNN) system, using 27 847 CE images (6503 images depicting blood content from 29 patients and 21 344 images of normal mucosa from 12 patients). We assessed its performance by calculating the area under the receiver operating characteristic curve (ROC-AUC) and its sensitivity, specificity, and accuracy, using an independent test set of 10 208 small-bowel images (208 images depicting blood content and 10 000 images of normal mucosa). The performance of the CNN was compared with that of the SBI, in individual image analysis, using the same test set., Results: The AUC for the detection of blood content was 0.9998. The sensitivity, specificity, and accuracy of the CNN were 96.63%, 99.96%, and 99.89%, respectively, at a cut-off value of 0.5 for the probability score, which were significantly higher than those of the SBI (76.92%, 99.82%, and 99.35%, respectively). The trained CNN required 250 s to evaluate 10 208 test images., Conclusions: We developed and tested the CNN-based detection system for blood content in CE images. This system has the potential to outperform the SBI system, and the patient-level analyses on larger studies are required., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The blood-cerebrospinal fluid barrier (BCSFB) is a highly dynamic transport interface that serves brain homeostasis. To date, however, understanding of its role in brain development and pathology has been hindered by the absence of a non-invasive technique for functional assessment. Here we describe a method for non-invasive measurement of BSCFB function by using tracer-free MRI to quantify rates of water delivery from arterial blood to ventricular cerebrospinal fluid. Using this method, we record a 36% decrease in BCSFB function in aged mice, compared to a 13% decrease in parenchymal blood flow, itself a leading candidate biomarker of early neurodegenerative processes. We then apply the method to explore the relationship between BCSFB function and ventricular morphology. Finally, we provide proof of application to the human brain. Our findings position the BCSFB as a promising new diagnostic and therapeutic target, the function of which can now be safely quantified using non-invasive MRI.

Studies have extensively analyzed the effect of hyperglycemia on 18 F-FDG uptake in normal tissues and tumors. In this study, we measured SUV in the brain, liver, and blood pool in normoglycemia, hyperglycemia, and hypoglycemia to understand the effect of blood glucose on 18 F-FDG uptake and to develop a formula to correct SUV. Methods: Whole-body 18 F-FDG PET/CT images of adults were selected for analysis. Brain SUV max , blood-pool SUV mean , and liver SUV mean were measured at blood glucose ranges of 61-70, 71-80, 81-90, 91-100, 101-110, 111-120, 121-130, 131-140, 141-150, 151-160, 161-170, 171-180, 181-190, 191-200, and 201 mg/dL and above. At each blood glucose range, 10 PET images were analyzed (total, 150). The mean (±SD) SUV of the brain, liver, and blood pool at each blood glucose range was calculated, and blood glucose and SUV curves were generated. Because brain and tumors show a high expression of glucose transporters 1 and 3, we generated an SUV correction formula based on percentage reduction in brain SUV max with increasing blood glucose level. Results: Mean brain SUV max gradually decreased with increasing blood glucose level, starting after a level of 110 mg/dL. The approximate percentage reduction in brain SUV max was 20%, 35%, 50%, 60%, and 65% at blood glucose ranges of 111-120, 121-140, 141-160, 161-200, and 201 mg/dL and above, respectively. In the formula we generated, measured SUV max is multiplied by a reduction factor of 1.25, 1.5, 2, 2.5, and 2.8 for the blood glucose ranges of 111-120, 121-140, 141-160, 161-200, and 201 mg/dL and above, respectively, to correct SUV. Brain SUV max did not differ between hypoglycemic and normoglycemic patients ( P > 0.05). SUV mean in the blood pool and liver was lower in hypoglycemic patients ( P < 0.05) and did not differ between hyperglycemic ( P > 0.05) and normoglycemic patients. Conclusion: Hyperglycemia gradually reduces brain 18 F-FDG uptake, starting after a blood glucose level of 110 mg/dL. Hyperglycemia does not affect 18 F-FDG activity in the liver or blood pool. Hypoglycemia does not seem to affect brain 18 F-FDG uptake but appears to reduce liver and blood-pool activity. The simple formula we generated can be used to correct SUV in hyperglycemic adults in selected cases., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Visualization of Indocyanine Green (ICG) near-infrared (NIR) fluorescence is a promising technique for biomedical applications because of its deep tissue penetration, low autofluorescence, weak dependence on ambient light, safety for patients and medical staff., Methods: To apply this technique to animal studies and clinical practice, we developed multispectral NIR fluorescence imaging system FLUM-808, which can be used in experimental studies and clinical practice, in open and endoscopic surgery (fluorescence-guided surgery). The object is illuminated either directly or through an illumination channel depending on what optical instrument is used (camera lens, fiber endoscope, rigid endoscope, surgical microscope, etc.). The system is able to simultaneously display NIR images and images captured under white light., Results: This article provides examples of imaging techniques used during open and endoscopic surgery with ICG as an NIR fluorescent dye and photosensitizer, demonstrates applications of the technique for experimental and clinical purposes: for intraoperative imaging of blood and lymphatic vessels; for detection of tumors and sentinel lymph nodes; for assessment of tissue, organ, or anastomotic blood supply., Conclusions: This method significantly helps to accurately assign the areas of increased fluorescence to certain anatomical structures during surgery. NIR fluorescence diagnosis can be used in important experimental studies and in clinical practice. The described results of ICG studies can help in developing new fluorescence-based diagnostic and theranostic approaches employing more effective exogenous fluorophores and photosensitizers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To characterize the diffusion coefficient of human blood for accurate results in intravoxel incoherent motion imaging., Methods: Diffusion-weighted MRI of blood samples from 10 healthy volunteers was acquired with a single-shot echo-planar-imaging sequence at body temperature. Effects of gradient profile (monopolar or flow-compensated), diffusion time (40-100 ms), and echo time (60-200 ms) were investigated., Results: Although measured apparent diffusion coefficients of blood were larger for flow-compensated than for monopolar gradients, no dependence of the apparent diffusion coefficient on the diffusion time was found. Large differences between individual samples were observed, with results ranging from 1.26 to 1.66 µm 2 /ms for flow-compensated and 0.94 to 1.52 µm 2 /ms for monopolar gradients. Statistical analysis indicates correlations of the flow-compensated apparent diffusion coefficient with hematocrit (P = 0.007) and hemoglobin (P = 0.017), but not with mean corpuscular volume (P = 0.64). Results of Monte-Carlo simulations support the experimental observations., Conclusions: Measured blood apparent diffusion coefficient values depend on hematocrit/hemoglobin concentration and applied gradient profile due to non-Gaussian diffusion. Because in vivo measurement is delicate, an estimation based on blood count results could be an alternative. For intravoxel incoherent motion modeling, the use of a blood self-diffusion constant D b  = 1.54 ± 0.12 µm 2 /ms for flow-compensated and D b  = 1.30 ± 0.18 µm 2 /ms for monopolar encoding is suggested. Magn Reson Med 79:2752-2758, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., (© 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc.)

Background: Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload., Methods: In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload., Results: The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms, r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1; among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1., Conclusions: In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.

Chemical Exchange Saturation Transfer (CEST) has been used to assess healthy and pathological tissue in both animals and humans. However, the CEST signal from blood has not been fully assessed. This paper presents the CEST and nuclear Overhauser enhancement (NOE) signals detected in human blood measured via z-spectrum analysis. We assessed the effects of blood oxygenation levels, haematocrit, cell structure and pH upon the z-spectrum in ex vivo human blood for different saturation powers at 7T. The data were analysed using Lorentzian difference (LD) model fitting and AREX (to compensate for changes in T 1 ), which have been successfully used to study CEST effects in vivo. Full Bloch-McConnell fitting was also performed to provide an initial estimate of exchange rates and transverse relaxation rates of the various pools. CEST and NOE signals were observed at 3.5 ppm, -1.7 ppm and -3.5 ppm and were found to originate primarily from the red blood cells (RBCs), although the amide proton transfer (APT) CEST effect, and NOEs showed no dependence upon oxygenation levels. Upon lysing, the APT and NOE signals fell significantly. Different pH levels in blood resulted in changes in both the APT and NOE (at -3.5 ppm), which suggests that this NOE signal is in part an exchange relayed process. These results will be important for assessing in vivo z-spectra., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop a dark blood-late gadolinium enhancement (DB-LGE) sequence that improves scar-blood contrast and delineation of scar region., Methods: The DB-LGE sequence uses an inversion pulse followed by T 2 magnetization preparation to suppress blood and normal myocardium. Time delays inserted after preparation pulses and T 2 -magnetization-prep duration are used to adjust tissue contrast. Selection of these parameters was optimized using numerical simulations and phantom experiments. We evaluated DB-LGE in 9 swine and 42 patients (56 ± 14 years, 33 male). Improvement in scar-blood contrast and overall image quality was subjectively evaluated by two independent readers (1 = poor, 4 = excellent). The signal ratios among scar, blood, and myocardium were compared., Results: Simulations and phantom studies demonstrated that simultaneous nulling of myocardium and blood can be achieved by selecting appropriate timing parameters. The scar-blood contrast score was significantly higher for DB-LGE (P < 0.001) with no significant difference in overall image quality (P > 0.05). Scar-blood signal ratios for DB-LGE versus LGE were 5.0 ± 2.8 versus 1.5 ± 0.5 (P < 0.001) for patients, and 2.2 ± 0.7 versus 1.0 ± 0.4 (P = 0.0023) for animals. Scar-myocardium signal ratios were 5.7 ± 2.9 versus 6.3 ± 2.6 (P = 0.35) for patients, and 3.7 ± 1.1 versus 4.1 ± 2.0 (P = 0.60) for swine., Conclusions: The DB-LGE sequence simultaneously reduces normal myocardium and blood signal intensity, thereby enhancing scar-blood contrast while preserving scar-myocardium contrast. Magn Reson Med 79:351-360, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Cardiopulmonary bypass procedures are one of the most common operations and blood oxygenators are the centre piece for the heart-lung machines. Blood oxygenators have been tested as entire devices but intricate details on the flow field inside the oxygenators remain unknown. In this study, a novel method is presented to analyse the flow field inside oxygenators based on micro Computed Tomography (μCT) scans. Two Hollow Fibre Membrane (HFM) oxygenator prototypes were scanned and three-dimensional full scale models that capture the device-specific fibre distributions are set up for computational fluid dynamics analysis. The blood flow through the oxygenator is modelled as a non-Newtonian fluid. The results were compared against the flow solution through an ideal fibre distribution and show the importance of a uniform distribution of fibres and that the oxygenators analysed are not susceptible to flow directionality as mass flow versus area remain the same. However the pressure drop across the oxygenator is dependent on flow rate and direction. By comparing residence time of blood against the time frame to fully saturate blood with oxygen we highlight the potential of this method as design optimisation tool. In conclusion, image-based reconstruction is found to be a feasible route to assess oxygenator performance through flow modelling. It offers the possibility to review a product as manufactured rather than as designed, which is a valuable insight as a precursor to the approval processes. Finally, the flow analysis presented may be extended, at computational cost, to include species transport in further studies., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hematogenous dissemination followed by tissue tropism is a characteristic of the infectious process of many pathogens including those transmitted by blood-feeding vectors. After entering into the blood circulation, these pathogens must arrest in the target organ before they infect a specific tissue. Here, we describe a non-invasive method to visualize and quantify the homing of pathogens to the host tissues. By using in vivo bioluminescence imaging we quantify the accumulation of luciferase-expressing parasites in the host organs during the first minutes following their intravascular inoculation in mice. Using this technique we show that in the malarial infection, once in the blood circulation, most of bioluminescent Plasmodium berghei sporozoites, the parasite stage transmitted to the host skin by a mosquito bite, rapidly home to the liver where they invade and develop inside hepatocytes. This homing is specific to this developmental stage since blood stage parasites do not accumulate in the liver, as well as extracellular Trypanosoma brucei bloodstream forms and liver-infecting Leishmania infantum amastigotes. Finally, this method can be used to study the dynamics of tissue tropism of parasites, dissect the molecular and cellular basis of their increased arrest in organs and to evaluate immune interventions designed to block this targeted interaction., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The assessment of the free water fraction in the brain provides important information about extracellular processes such as atrophy and neuroinflammation in various clinical conditions as well as in normal development and aging. Free water estimates from diffusion MRI are assumed to account for freely diffusing water molecules in the extracellular space, but may be biased by other pools of molecules in rapid random motion, such as the intravoxel incoherent motion (IVIM) of blood, where water molecules perfuse in the randomly oriented capillary network. The goal of this work was to separate the signal contribution of the perfusing blood from that of free-water and of other brain diffusivities. The influence of the vascular compartment on the estimation of the free water fraction and other diffusivities was investigated by simulating perfusion in diffusion MRI data. The perfusion effect in the simulations was significant, especially for the estimation of the free water fraction, and was maintained as long as low b-value data were included in the analysis. Two approaches to reduce the perfusion effect were explored in this study: (i) increasing the minimal b-value used in the fitting, and (ii) using a three-compartment model that explicitly accounts for water molecules in the capillary blood. Estimation of the model parameters while excluding low b-values reduced the perfusion effect but was highly sensitive to noise. The three-compartment model fit was more stable and additionally, provided an estimation of the volume fraction of the capillary blood compartment. The three-compartment model thus disentangles the effects of free water diffusion and perfusion, which is of major clinical importance since changes in these components in the brain may indicate different pathologies, i.e., those originating from the extracellular space, such as neuroinflammation and atrophy, and those related to the vascular space, such as vasodilation, vasoconstriction and capillary density. Diffusion MRI data acquired from a healthy volunteer, using multiple b-shells, demonstrated an expected non-zero contribution from the blood fraction, and indicated that not accounting for the perfusion effect may explain the overestimation of the free water fraction evinced in previous studies. Finally, the applicability of the method was demonstrated with a dataset acquired using a clinically feasible protocol with shorter acquisition time and fewer b-shells., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To study the feasibility of black-blood contrast in native T 1 mapping for reduction of partial voluming at the blood-myocardium interface., Methods: A saturation pulse prepared heart-rate-independent inversion recovery (SAPPHIRE) T 1 mapping sequence was combined with motion-sensitized driven-equilibrium (MSDE) blood suppression for black-blood T 1 mapping at 3 Tesla. Phantom scans were performed to assess the T 1 time accuracy. In vivo black-blood and conventional SAPPHIRE T 1 mapping was performed in eight healthy subjects and analyzed for T 1 times, precision, and inter- and intraobserver variability. Furthermore, manually drawn regions of interest (ROIs) in all T 1 maps were dilated and eroded to analyze the dependence of septal T 1 times on the ROI thickness., Results: Phantom results and in vivo myocardial T 1 times show comparable accuracy with black-blood compared to conventional SAPPHIRE (in vivo: black-blood: 1562 ± 56 ms vs. conventional: 1583 ± 58 ms, P = 0.20); Using black-blood SAPPHIRE precision was significantly lower (standard deviation: 133.9 ± 24.6 ms vs. 63.1 ± 6.4 ms, P < .0001), and blood T 1 time measurement was not possible. Significantly increased interobserver interclass correlation coefficient (ICC) (0.996 vs. 0.967, P = 0.011) and similar intraobserver ICC (0.979 vs. 0.939, P = 0.11) was obtained with the black-blood sequence. Conventional SAPPHIRE showed strong dependence on the ROI thickness (R 2 = 0.99). No such trend was observed using the black-blood approach (R 2 = 0.29)., Conclusion: Black-blood SAPPHIRE successfully eliminates partial voluming at the blood pool in native myocardial T 1 mapping while providing accurate T 1 times, albeit at a reduced precision. Magn Reson Med 78:484-493, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: To develop a fast protocol for measuring T 1 values in the internal carotid artery (ICA), to validate this technique with in vitro measurements, and to evaluate its reproducibility., Methods: A modified Look-Locker sequence was optimized to enable rapid determination of T 1 in the ICA at 3T. T 1 values from the ICA were compared with in vitro measurements on individually sampled venous blood oxygenated to arterial levels. A test-retest reproducibility study was also conducted., Results: The group-averaged arterial blood T 1 value was 1908 ± 77 ms for six women (hematocrit = 0.39 ± 0.03) and 1785 ± 55 ms for seven men (hematocrit = 0.45 ± 0.02), which is 100-200 ms longer than the widely adopted value obtained from bovine blood experiments. The arterial T 1 value per subject correlated significantly with individual hematocrit values. The intrasession and intersession coefficients of variation were 1.1% and 2.1%, respectively, indicating good precision and reproducibility of our method. Reasonable agreement was observed between the in vivo and in vitro results with a correlation coefficient of 0.78., Conclusion: The proposed method can provide fast arterial T 1 measurement on individual subjects. When not performing such a subject-specific measurement, we recommend the use of 1908 ms and 1785 ms for healthy women and men, respectively, or 1841 ms for adults in general. Magn Reson Med 77:2296-2302, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: To determine if intracranial hemorrhages (ICH) are always hypointense on Susceptibility weighted imaging (SWI) and to determine the effect of T1-signal intensity on the appearance of ICH in SWI series., Methods: SWI and T1-signal intensities of ICH were retrospectively studied in a series of patients. SWI signal intensities were statistically correlated with T1-signal intensities., Results: In a series of 57 MRI scans from 40 patients, ICH was hypointense in 19, mixed-intensity in 21, and hyperintense in 17. Hyperintensity of ICH on SWI was significantly associated with increased T1 signal (P<.001)., Conclusion: ICH can have a varied appearance on SWI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: X-ray phase-contrast imaging (PCI) provides additional information beyond absorption characteristics by detecting the phase shift of the X-ray beam passing through material. The grating-based system works with standard polychromatic X-ray sources, promising a possible clinical implementation. PCI has been shown to provide additional information in soft-tissue samples. The aim of this study was to determine if ex vivo quantitative phase-contrast computed tomography (PCCT) may differentiate between pathologic fluid collections., Materials and Methods: PCCT was performed with the grating interferometry method. A protein serial dilution, human blood samples and 17 clinical samples of pathologic fluid retentions were imaged and correlated with clinical chemistry measurements. Conventional and phase-contrast tomography images were reconstructed. Phase-contrast Hounsfield Units (HUp) were used for quantitative analysis analogously to conventional HU. The imaging was analyzed using overall means, ROI values as well as whole-volume-histograms and vertical gradients. Contrast to noise ratios were calculated between different probes and between imaging methods., Results: HUp showed a very good linear correlation with protein concentration in vitro. In clinical samples, HUp correlated rather well with cell count and triglyceride content. PCI was better than absorption imaging at differentiating protein concentrations in the protein samples as well as at differentiating blood plasma from cellular components. PCI also allowed for differentiation of watery samples (such as lymphoceles) from pus., Conclusion: Phase-contrast computed tomography is a promising tool for the differentiation of pathologic fluids that appear homogenous with conventional attenuation imaging., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

We propose two automatic methods for detecting bleeding in wireless capsule endoscopy videos of the small intestine. The first one uses solely the color information, whereas the second one incorporates the assumptions about the blood spot shape and size. The original idea is namely the definition of a new color space that provides good separability of blood pixels and intestinal wall. Both methods can be applied either individually or their results can be fused together for the final decision. We evaluate their individual performance and various fusion rules on real data, manually annotated by an endoscopist.

Purpose: To determine the contribution of paramagnetic dissolved oxygen in blood plasma to blood-oxygenation-level-dependent (BOLD) signal changes in hyperoxic calibrated BOLD studies., Methods: Bovine blood plasma samples were prepared with partial pressures of oxygen (pO 2 ) ranging from 110 to 600 mmHg. R 1 , R 2 , and R 2 * of the plasma with dissolved oxygen were measured using quantitative MRI sequences at 3 Tesla. Simulations were performed to predict the relative effects of dissolved oxygen and deoxyhemoglobin changes in hyperoxia calibrated BOLD., Results: The relaxivities of dissolved oxygen in plasma were found to be r 1, O2 =1.97 ± 0.09 ×10 -4 s -1 mmHg -1 , r 2, O2 =2.3 ± 0.7 ×10 -4 s -1 mmHg -1 , and r 2, O2 * = 2.3 ± 0.7 ×10 -4 s -1 mmHg -1 . Simulations predict that neither the transverse nor longitudinal relaxation rates of dissolved oxygen contribute significantly to the BOLD signal during hyperoxia., Conclusion: During hyperoxia, the increases in R 2 and R 2 * of blood from dissolved oxygen in plasma are considerably less than the decreases in R 2 and R 2 * from venous deoxyhemoglobin. R 1 effects due to dissolved oxygen are also predicted to be negligible. As a result, dissolved oxygen in arteries should not contribute significantly to the hyperoxic calibrated BOLD signal. Magn Reson Med 76:1905-1911, 2016. © 2015 International Society for Magnetic Resonance in Medicine., (© 2015 International Society for Magnetic Resonance in Medicine.)

The objective of this work was to investigate the influence of the definition of blood as a distinct source on organ doses, associated with the administration of a novel radiopharmaceutical for positron emission tomography-computed tomography (PET/CT) imaging-(S)-4-(3- 18 F-fluoropropyl)-L-glutamic acid ( 18 F-FSPG). Personalised pharmacokinetic models were constructed based on clinical PET/CT images from five healthy volunteers and blood samples from four of them. Following an identifiability analysis of the developed compartmental models, person-specific model parameters were estimated using the commercial program SAAM II. Organ doses were calculated in accordance to the formalism promulgated by the Committee on Medical Internal Radiation Dose (MIRD) and the International Commission on Radiological Protection (ICRP) using specific absorbed fractions for photons and electrons previously derived for the ICRP reference adult computational voxel phantoms. Organ doses for two concepts were compared: source organ activities in organs parenchyma with blood as a separate source (concept-1); aggregate activities in perfused source organs without blood as a distinct source (concept-2). Aggregate activities comprise the activities of organs parenchyma and the activity in the regional blood volumes (RBV). Concept-1 resulted in notably higher absorbed doses for most organs, especially non-source organs with substantial blood contents, e.g. lungs (92% maximum difference). Consequently, effective doses increased in concept-1 compared to concept-2 by 3-10%. Not considering the blood as a distinct source region leads to an underestimation of the organ absorbed doses and effective doses. The pronounced influence of the blood even for a radiopharmaceutical with a rapid clearance from the blood, such as 18 F-FSPG, suggests that blood should be introduced as a separate compartment in most compartmental pharmacokinetic models and blood should be considered as a distinct source in dosimetric calculations. Hence, blood samples should be included in all pharmacokinetic and dosimetric studies for new tracers if possible.

The polyelectrolyte microcapsules that can be accurate either visualized in biological media or in tissue would enhance their further in vivo application both as a carrier of active payloads and as a specific sensor. The immobilization of active species, for instance fluorescent dyes, quantum dots, metal nanoparticles, in polymeric shell enables visualization of capsules by optical imaging techniques in aqueous solution. However, for visualization of capsules in complex media an instrument with high contrast modality requires. Herein, we show for the first time photoacoustic imaging (PAI) of multifunctional microcapsules in water and in blood. The microcapsules exhibit greater photoacoustic intensity compare to microparticles with the same composition of polymeric shell presumably their higher thermal expansion. Photoacoustic intensity form microcapsules dispersed in blood displays an enhancement (2-fold) of signal compare to blood. Photoacoustic imaging of microcapsules might contribute to non-invasive carrier visualization and further their in vivo distribution., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Several variables may affect the local contrast values in laser speckle contrast imaging (LSCI), irrespective of relative motion. It has been suggested that the optical properties of the moving fluid and surrounding tissues can affect LSCI values. However, a detailed study of this has yet to be presented. In this work, we examined the combined effects of the reduced scattering and absorption coefficients on LSCI. This study employs fluid phantoms with different optical properties that were developed to mimic whole blood with varying hematocrit levels. These flow phantoms were imaged with an LSCI system developed for this study. The only variable parameter was the optical properties of the flowing fluid. A negative linear relationship was seen between the changes in contrast and changes in reduced scattering coefficient, absorption coefficient, and total attenuation coefficient. The change in contrast observed due to an increase in the scattering coefficient was greater than what was observed with an increase in the absorption coefficient. The results indicate that optical properties affect contrast values and that they should be considered in the interpretation of LSCI data.

In this paper, we follow the thermodynamic theory with internal variables of Kluitenberg evaluating the entropy production of red blood cell in saline solution and whole blood, respectively, when they are subjected to an ultrasound wave. From a thermodynamic point of view, blood is an open system; so to fully represent the entropy variation as function of frequency perturbation we employ phenomenological coefficients which allow us to qualitatively discriminate among classes of phenomena which cannot be observed in any other way. Therefore, a correlation between these coefficients and quantities experimentally measurable allows to a deeper knowledge of biological phenomena., Competing Interests: The authors declare that they have no conflict of interest. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.

The objective of this study was to develop and demonstrate a technique to eliminate venous enhancement in contrast-enhanced magnetic resonance lymphangiography through shortening T2(⁎) in the blood pool, thus allowing for a lymphatic-only map. Administration of the blood-pool iron agent ferumoxtyol in addition to intracutaneous gadolinium during contrast-enhanced magnetic resonance lymphangiography allows for suppression of vascular structures to achieve venous-free lymphatic mapping., (Copyright © 2015 Mosby, Inc. All rights reserved.)

This study was conducted to assess time-sensitive magnetic resonance (MR) changes in canine blood using low-field MR. Arterial and venous blood samples were collected from eight healthy beagle dogs. Samples were placed in 5-mL tubes and imaged within 3 hours of collection at 1 day intervals from day 1 to day 30. The following sequences were used: T1-weighted (T1W), T2-weighted (T2W), fluid-attenuated inversion recovery (FLAIR), short tau inversion recovery (STIR), and T2-star gradient-echo (T2(*)-GRE). Visual comparison of the images revealed that four relatively homogenous blood clots and twelve heterogeneous blood clots developed. The margination of the clot and plasma changed significantly on day 2 and day 13. On day 2, heterogeneous blood clots were differentiated into 2 to 3 signal layers in the T2W, T1W, and especially the STIR images. Hypointense signal layers were also detected in the blood clots in STIR images, which have T2 hypo, FLAIR hypo, and T1 hyper intense signals. In all images, these signal layers remained relatively unchanged until day 13. Overall, the results suggest that hematomas are complex on low-field MRI. Accordingly, it may not be feasible to accurately characterize hemorrhages and predict clot age based on low-field MRI.

Background: Pixel-level tissue classification for ultrasound images, commonly applied to carotid images, is usually based on defining thresholds for the isolated pixel values. Ranges of pixel values are defined for the classification of each tissue. The classification of pixels is then used to determine the carotid plaque composition and, consequently, to determine the risk of diseases (e.g., strokes) and whether or not a surgery is necessary. The use of threshold-based methods dates from the early 2000s but it is still widely used for virtual histology., Methodology/principal Findings: We propose the use of descriptors that take into account information about a neighborhood of a pixel when classifying it. We evaluated experimentally different descriptors (statistical moments, texture-based, gradient-based, local binary patterns, etc.) on a dataset of five types of tissues: blood, lipids, muscle, fibrous, and calcium. The pipeline of the proposed classification method is based on image normalization, multiscale feature extraction, including the proposal of a new descriptor, and machine learning classification. We have also analyzed the correlation between the proposed pixel classification method in the ultrasound images and the real histology with the aid of medical specialists., Conclusions/significance: The classification accuracy obtained by the proposed method with the novel descriptor in the ultrasound tissue images (around 73%) is significantly above the accuracy of the state-of-the-art threshold-based methods (around 54%). The results are validated by statistical tests. The correlation between the virtual and real histology confirms the quality of the proposed approach showing it is a robust ally for the virtual histology in ultrasound images.

Blood-filled cysts (BFC) within the heart are common findings at postmortem examinations of fetuses and infants. However, such cysts are very rare entities in adolescents and adults. We report here an adult case of BFC attached to the posterior leaflet of the tricuspid valve, demonstrating the importance of multimodal diagnostic imaging combining both echocardiography and magnetic resonance imaging., (© 2015, Wiley Periodicals, Inc.)

Histotripsy thrombolysis is a non-invasive, drug-free, image-guided therapy that fractionates blood clots using well-controlled acoustic cavitation alone. Real-time quantitative feedback is highly desired during histotripsy thrombolysis treatment to monitor the progress of clot fractionation. Bubble-induced color Doppler (BCD) monitors the motion after cavitation generated by each histotripsy pulse, which has been found in gel and ex vivo liver tissue to be correlated with histotripsy fractionation. We investigated the potential of BCD to quantitatively monitor histotripsy thrombolysis in real time. To visualize clot fractionation, transparent three-layered fibrin clots were developed. Results indicated that a coherent motion follows the cavitation generated by each histotripsy pulse with a push and rebound pattern. The temporal profile of this motion expands and saturates as treatment progresses. A strong correlation exists between the degree of histotripsy clot fractionation and two metrics extracted from BCD: time of peak rebound velocity (tPRV) and focal mean velocity at a fixed delay (Vf,delay). The saturation of clot fractionation (i.e., treatment completion) matches well the saturations detected using tPRV and Vf,delay. The mean Pearson correlation coefficients between the progression of clot fractionation and the two BCD metrics were 93.1% and 92.6%, respectively. To validate BCD feedback in in vitro clots, debris volumes from histotripsy thrombolysis were obtained at different therapy doses and compared with Vf,delay. There is also good agreement between the increasing and saturation trends of debris volume and Vf,delay. Finally, a real-time BCD feedback algorithm to predict complete clot fractionation during histotripsy thrombolysis was developed and tested. This work illustrates the potential of BCD to monitor histotripsy thrombolysis treatment in real time., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The mechanical index (MI) attempts to quantify the likelihood that exposure to diagnostic ultrasound will produce an adverse biological effect by a non-thermal mechanism. The current formulation of the MI implicitly assumes that the acoustic field is generated using the short pulse durations appropriate to B-mode imaging. However, acoustic radiation force impulse (ARFI) imaging employs high-intensity pulses up to several hundred acoustic periods long. The effect of increased pulse durations on the thresholds for inertial cavitation was studied computationally in water, urine, blood, cardiac and skeletal muscle, brain, kidney, liver and skin. The results indicate that, although the effect of pulse duration on cavitation thresholds in the three liquids can be considerable, reducing them by, for example, 6%-24% at 1 MHz, the effect on tissue is minor. More importantly, the frequency dependence of the MI appears to be unnecessarily conservative; that is, the magnitude of the exponent on frequency could be increased to 0.75. Comparison of these theoretical results with experimental measurements suggests that some tissues do not contain the pre-existing, optimally sized bubbles assumed for the MI. This means that in these tissues, the MI is not necessarily a strong predictor of the probability of an adverse biological effect., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The purpose of the present study was to evaluate the ranges of Hounsfield unit (HU) found in body fluids, putrefaction fluids, and blood on postmortem CT and how these ranges are affected by postmortem interval, temperatures, and CT beam energy. Body fluids, putrefaction fluids, and blood from a total of 53 corpses were analyzed to determine the ranges of HU values from postmortem CT images that were taken prior to autopsy. The fluids measured in CT images were obtained at autopsy and examined in terms of macroscopic and microscopic appearances. Body fluids and blood were also collected in plastic bottles, which were subjected to CT scans at different beam energies (80-130 kV) and at various fluid temperatures (4 to 40 °C). At a postmortem interval of 1 to 4 days, the ranges of HU values of the serous fluids (13-38 HU) and the nonsedimented blood (40-88 HU) did not overlap. In the sedimented blood, the upper serum layer exhibited HU value ranges that overlapped with those of the serous fluids. The putrefaction fluids exhibited a range of HU values between 80 and -130 HU. Elevated HU values were observed in fluids with accretive cell impurities. HU values decreased slightly with increasing temperature and CT beam energy. We concluded that serous fluids and blood in fresh corpses can be characterized and differentiated from each other based on HU value ranges. In contrast, body fluids in decomposed corpses cannot be differentiated by their HU value ranges. Different beam energies and corpse temperatures had only minor influences on HU value ranges and therefore should not be obstacles to the differentiation and characterization of body fluids and blood.

For automated segmentation of 3-D echocardiographic images, incorporation of temporal information may be helpful. In this study, optimal settings for calculation of temporal cross-correlations between subsequent time frames were determined, to obtain the maximum cross-correlation (MCC) values that provided the best contrast between blood and cardiac tissue over the entire cardiac cycle. Both contrast and boundary gradient quality measures were assessed to optimize MCC values with respect to signal choice (radiofrequency or envelope data) and axial window size. Optimal MCC values were incorporated into a deformable model to automatically segment the left ventricular cavity. MCC values were tested against, and combined with, filtered, demodulated radiofrequency data. Results reveal that using envelope data in combination with a relatively small axial window (0.7-1.25 mm) at fine scale results in optimal contrast and boundary gradient between the two tissues over the entire cardiac cycle. Preliminary segmentation results indicate that incorporation of MCC values has additional value for automated segmentation of the left ventricle., (Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Blood flow speed is an important functional parameter. Doppler ultrasound flowmetry lacks sufficient sensitivity to slow blood flow (several to tens of millimeters per second) in deep tissue. To address this challenge, we developed ultrasonically encoded photoacoustic flowgraphy combining ultrasonic thermal tagging with photoacoustic imaging. Focused ultrasound generates a confined heat source in acoustically absorptive fluid. Thermal waves propagate with the flow and are directly visualized in pseudo color using photoacoustic computed tomography. The Doppler shift is employed to calculate the flow speed. This method requires only acoustic and optical absorption, and thus is applicable to continuous fluid. A blood flow speed as low as 0.24  mm·s(-1)} was successfully measured. Deep blood flow imaging was experimentally demonstrated under 5-mm-thick chicken breast tissue.

Ultrasonic backscattered signals from blood contain frequency-dependent information that can be used to obtain quantitative parameters reflecting the aggregation level of red blood cells (RBCs). The approach is based on estimating structural aggregate parameters by fitting the spectrum of the backscattered radio-frequency echoes from blood to an estimated spectrum considering a theoretical scattering model. In this study, three scattering models were examined: a new implementation of the Gaussian model (GM), the structure factor size estimator (SFSE), and the new effective medium theory combined with the structure factor model (EMTSFM). The accuracy of the three scattering models in determining mean aggregate size and compactness was compared by 2-D and 3-D computer simulations in which RBC structural parameters were controlled. Two clustering conditions were studied: 1) the aggregate size varied and the aggregate compactness was fixed in both 2-D and 3-D cases, and 2) the aggregate size was fixed and the aggregate compactness varied in the 2-D case. For both clustering conditions, the EMTSFM was found to be more suitable than GM and SFSE for characterizing RBC aggregation.

The assessment of coagulating blood elasticity has gained importance as a result of several studies that have correlated it to cardiovascular pathologic conditions. In this study we use supersonic shear wave imaging (SSI) to measure viscoelastic properties of blood clots. At the same time, classical rheometry experiments were carried out on the same blood samples taken within the first few seconds of coagulation. Using SSI, phase velocities of the shear wave indicated increasing dispersion with time. In all cases, the frequency bandwidth of propagating shear waves changed from 20-50 Hz at the first few min of coagulation to around 300 Hz toward the end of experiments. Using the values of G' and G″ from the rheometry studies, the theoretical shear wave velocities were calculated and correlated with SSI measurements. Results of the two techniques were in very good agreement, confirming that SSI provides accurate measurements of viscoelastic properties as corroborated by conventional rheometric measurements., (Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Previous studies have found that ultrasound backscatter from blood in vascular flow systems varies under pulsatile flow, with the maximum values occurring during the systolic period. This phenomenon is of particular interest in hemorheology because it is contrary to the well-known fact that red blood cell (RBC) aggregation, which determines the intensity of ultrasound backscatter from blood, decreases at a high systolic shear rate. In the present study, a rat model was used to provide basic information on the characteristics of blood echogenicity in arterial blood flow to investigate the phenomenon of RBC aggregation under pulsatile flow. Blood echogenicity in the common carotid arteries of rats was measured using a high-frequency ultrasound imaging system with a 40-MHz probe. The electrocardiography-based kilohertz visualization reconstruction technique was employed to obtain high-temporal-resolution and high-spatial-resolution time-course B-mode cross-sectional and longitudinal images of the vessel. The experimental results indicate that blood echogenicity in rat carotid arteries varies during a cardiac cycle. Blood echogenicity tends to decrease during early systole and reaches its peak during late systole, followed by a slow decline thereafter. The time delay of the echogenicity peak from peak systole in the present results is the main difference from previous in vitro and in vivo observations of backscattering peaks during early systole, which may be caused by the very rapid heart rates and low RBC aggregation tendency of rats compared with humans and other mammalian species. The present study may provide useful information elucidating the characteristics of RBC aggregation in arterial blood flow., (Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Intravascular near-infrared fluorescence (NIRF) imaging offers a new approach for characterizing atherosclerotic plaque, but random catheter positioning within the vessel lumen results in variable light attenuation and can yield inaccurate measurements. We hypothesized that NIRF measurements could be corrected for variable light attenuation through blood by tracking the location of the NIRF catheter with intravascular ultrasound (IVUS). In this study, a combined NIRF-IVUS catheter was designed to acquire coregistered NIRF and IVUS data, an automated image processing algorithm was developed to measure catheter-to-vessel wall distances, and depth-dependent attenuation of the fluorescent signal was corrected by an analytical light propagation model. Performance of the catheter sensing distance correction method was evaluated in coronary artery phantoms and ex vivo arteries. The correction method produced NIRF estimates of fluorophore concentrations, in coronary artery phantoms, with an average root mean square error of 17.5%. In addition, the correction method resulted in a statistically significant improvement in correlation between spatially resolved NIRF measurements and known fluorophore spatial distributions in ex vivo arteries (from r = 0.24 to 0.69, p < 0.01, n = 6). This work demonstrates that catheter-to-vessel wall distances, measured from IVUS images, can be employed to compensate for inaccuracies caused by variable intravascular NIRF sensing distances.

The ongoing expansion of the frequency range used for ultrasonic imaging requires increasing attention to the acoustic attenuation of biomaterials. This work presents a novel method for measuring the attenuation of tissue and liquids in vitro on the basis of single transmission measurements. Ultrasound was generated by short laser pulses directed onto a silicon wafer. In addition, unfocused piezoelectric transducers with a center frequency of 50 MHz were used to detect and emit ultrasound. The laser ultrasound method produces signals with a peak frequency of 30 MHz. In comparison to piezoelectric generation, pulse laser excitation provides approximately 4 times higher amplitudes and 20% larger bandwidth. By using two excitation methods in succession, the attenuation parameters of porcine fat samples with thicknesses in the range of 1.5 to 20 mm could be determined quantitatively within a total frequency range of 5 to 45 MHz. The setup for liquid measurements was tested on samples of human blood and olive oil. Our results are in good agreement with reports in literature.

Thrombosis, or malignant blood clotting, is associated with numerous cardiovascular diseases and cancers. A microbubble contrast agent is presented that produces ultrasound harmonic signal only when exposed to elevated thrombin levels. Initially silent microbubbles are activated in the presence of both thrombin-spiked and freshly clotting blood in three minutes with detection limits of 20 nM thrombin and 2 aM microbubbles., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

New radiotracer developments for nuclear medicine imaging require the analysis of blood as a function of time in small animal models. A microfluidic device was developed to monitor the radioactivity concentration in the blood of rats and mice in real time. The microfluidic technology enables a large capture solid angle and a reduction in the separation distance between the sample and detector, thus increasing the detection efficiency. This in turn allows a reduction of the required detection volume without compromising sensitivity, an important advantage with rodent models having a small total blood volume (a few ml). A robust fabrication process was developed to manufacture the microchannels on top of unpackaged p-i-n photodiodes without altering detector performance. The microchannels were fabricated with KMPR, an epoxy-based photoresist similar to SU-8 but with improved resistance to stress-induced fissuring. Surface passivation of the KMPR enables non-diluted whole blood to flow through the channel for up to 20 min at low speed without clotting. The microfluidic device was embedded in a portable blood counter with dedicated electronics, pumping unit and computer control software for utilisation next to a small animal nuclear imaging scanner. Experimental measurements confirmed model predictions and showed a 4- to 19-fold improvement in detection efficiency over existing catheter-based devices, enabling a commensurate reduction in sampled blood volume. A linear dose-response relationship was demonstrated for radioactivity concentrations typical of experiments with rodents. The system was successfully used to measure the blood input function of rats in real time after radiotracer injection.

Positron emission tomography (PET) can be used to quantify physiological parameters. However to perform quantification requires that an input function is measured, namely a plasma time activity curve (TAC). Image-derived input functions (IDIFs) are attractive because they are noninvasive and nearly no blood loss is involved. However, the spatial resolution and the signal to noise ratio (SNR) of PET images are low, which degrades the accuracy of IDIFs. The objective of this study was to extract accurate input functions from microPET images with zero or one plasma sample using wavelet packet based sub-band decomposition independent component analysis (WP SDICA). Two approaches were used in this study. The first was the use of simulated dynamic rat images with different spatial resolutions and SNRs, and the second was the use of dynamic images of eight Sprague-Dawley rats. We also used a population-based input function and a fuzzy c-means clustering approach and compared their results with those obtained by our method using normalized root mean square errors, area under curve errors, and correlation coefficients. Our results showed that the accuracy of the one-sample WP SDICA approach was better than the other approaches using both simulated and realistic comparisons. The errors in the metabolic rate, as estimated by one-sample WP SDICA, were also the smallest using our approach., (Copyright © 2012 Elsevier Inc. All rights reserved.)