Gastrointestinal Bleeding Scintigraphy in the Early 21st Century.

Gastrointestinal bleeding scintigraphy performed with (99m)Tc-labeled autologous erythrocytes or historically with (99m)Tc-sulfur colloid has been a clinically useful tool since the 1970s. This article reviews the history of the techniques, the different methods of radiolabeling erythrocytes, the procedure, useful indications, diagnostic accuracy, the use of SPECT/CT and CT angiography to evaluate gastrointestinal bleeding, and Meckel diverticulum imaging. The causes of pediatric bleeding are discussed by age.

Technetium-99m labelled red blood cells scintigraphy and not iminodiacetic acid cholescintigraphy facilitates the discrimination of hepatic cirrhosis from fibrosis.

OBJECTIVE: This pilot study was designed to investigate the efficacy of technetium-99m labelled red blood cells ((99m)Tc-RBC) compared with (99m)Tc-mebrofenin cholescintigraphy ((99m)Tc-MHS), in the diagnosis of hepatic dysfunction at early stages. SUBJECTS AND METHODS: Twenty four patients, 8 with hepatic fibrosis and 16 with cirrhosis, at Child-Pugh stage A to C and 20 age-matched controls were examined by (99m)Tc-RBC and by (99m)Tc-MHS. Dynamic acquisition and static images were semiquantitatively analused by studying the liver-to-heart (L/H) ratio estimated by both the (99m)Tc-RBC and (99m)Tc-MHS methods. The L/H ratios were compared between fibrosis, cirrhotic stages and controls, by Student's t test. Linear regression analysis of the L/H ratios for both methods has been applied in the whole study population. RESULTS: Labelled RBC could statistically differentiate fibrotic from normal liver parenchyma (P<0.001), whereas the (99m)Tc-MHS could not (P: 0.13). The L/H ratios of cirrhotic lesions using both methods were significantly lower than those in controls: (P<0.000001 for (99m)Tc-RBC and P<0.0001 for (99m)Tc-MHS). Statistically significant difference was demonstrated by both modalities between fibrotic and cirrhotic lesions ((99m)Tc-RBC: P: 0.003 and (99m)Tc-MHS: P: 0.024). CONCLUSION: Our study although in a limited number of patients suggested that as opposed to (99m)Tc-MHS, scintigraphic evaluation by (99m)Tc-RBC could be useful in the discrimination of patients with liver fibrosis, cirrhosis and normal controls.

Experimental application of ultrafast imaging to spectral tissue characterization.

Ultrasound ultrafast imaging (UI) allows acquisition of thousands of frames per second with a sustained image quality at any depth in the field of view. Therefore, it would be ideally suited to obtain good statistical sampling of fast-moving tissues using spectral-based techniques to derive the backscatter coefficient (BSC) and associated quantitative parameters. In UI, an image is formed by insonifying the medium with plane waves steered at different angles, beamforming them and compounding the resulting radiofrequency images. We aimed at validating, experimentally, the effect of these beamforming protocols on the BSC, under both isotropic and anisotropic conditions. Using UI techniques with a linear array transducer (5-14 MHz), we estimated the BSCs of tissue-mimicking phantoms and flowing porcine blood at depths up to 35 mm with a frame rate reaching 514 Hz. UI-based data were compared with those obtained using single-element transducers and conventional focusing imaging. Results revealed that UI compounded images can produce valid estimates of BSCs and effective scatterer size (errors less than 2.2 ± 0.8 and 0.26 ± 0.2 dB for blood and phantom experiments, respectively). This work also describes the use of pre-compounded UI images (i.e., steered images) to assess the angular dependency of circulating red blood cells. We have concluded that UI data sets can be used for BSC spectral tissue analysis and anisotropy characterization.

Preparation and radiochemical control of 99mTc labeled blood pool agent for in vivo labelling of the red blood cells.

Our aim was to prepare cheap blood pool imaging kits by simplified method to overcome the burden on purchase department of MINAR, Nishtar Hospital, Multan, Pakistan. Secondarily, prompt supply of kits should save the time of patient during transportation. A total of 24 subjects selected for this study were equally divided into two groups. Mixture of stannous chloride and sodium pyrophosphate solution at pH 7 was injected to these subjects. Various concentrations (ranging from 200 to 800 microg) of stannous chloride dihydrate were injected to group one, followed by intravenous administration of technetium-99m (99mTc) pertechnetate at 30 min interval in 12 subjects. Labeling percentage of each sample was calculated afterwards followed by imaging under gamma camera. Each parameter was tested on three different patients and average of these three was calculated. In second set of experiments done on group two the same procedure was repeated in another 12 subjects, while keeping the concentration of Sn PYP constant at 400 microg. In this case, 99mTc was administered at different time intervals in different subjects ranging from 15 to 120 min (15, 30, 60 and 120 min) followed by calculation of labeling percentage and imaging under gamma camera. In group one, average percentage values of binding of red blood cells with 99mTc were 23.24, 84.88, 83.78 and 60.33% for concentrations of 200, 400, 600 and 800 microg, respectively. In group two, average percentage binging values of 22.26, 84.36. 55.54 and 28.67% were calculated at time intervals of 15, 30, 60 and 120 min, respectively. It is concluded from the results that the best blood pool imaging under gamma camera was observed for the concentration of 400 microg and the time interval of 30 min. The maximum percentage binding of red blood cells with 99mTc was calculated at concentration of 400 microg after 30 min interval that also correlated with imaging results.

MANTiS: a program for the analysis of X-ray spectromicroscopy data.

Spectromicroscopy combines spectral data with microscopy, where typical datasets consist of a stack of images taken across a range of energies over a microscopic region of the sample. Manual analysis of these complex datasets can be time-consuming, and can miss the important traits in the data. With this in mind we have developed MANTiS, an open-source tool developed in Python for spectromicroscopy data analysis. The backbone of the package involves principal component analysis and cluster analysis, classifying pixels according to spectral similarity. Our goal is to provide a data analysis tool which is comprehensive, yet intuitive and easy to use. MANTiS is designed to lead the user through the analysis using story boards that describe each step in detail so that both experienced users and beginners are able to analyze their own data independently. These capabilities are illustrated through analysis of hard X-ray imaging of iron in Roman ceramics, and soft X-ray imaging of a malaria-infected red blood cell.

Chronic assessment of cerebral hemodynamics during rat forepaw electrical stimulation using functional ultrasound imaging.

Functional ultrasound imaging is a method recently developed to assess brain activity via hemodynamics in rodents. Doppler ultrasound signals allow the measurement of cerebral blood volume (CBV) and red blood cells' (RBCs') velocity in small vessels. However, this technique originally requires performing a large craniotomy that limits its use to acute experiments only. Moreover, a detailed description of the hemodynamic changes that underlie functional ultrasound imaging has not been described but is essential for a better interpretation of neuroimaging data. To overcome the limitation of the craniotomy, we developed a dedicated thinned skull surgery for chronic imaging. This procedure did not induce brain inflammation nor neuronal death as confirmed by immunostaining. We successfully acquired both high-resolution images of the microvasculature and functional movies of the brain hemodynamics on the same animal at 0, 2, and 7 days without loss of quality. Then, we investigated the spatiotemporal evolution of the CBV hemodynamic response function (HRF) in response to sensory-evoked electrical stimulus (1 mA) ranging from 1 (200 µs) to 25 pulses (5s). Our results indicate that CBV HRF parameters such as the peak amplitude, the time to peak, the full width at half-maximum and the spatial extent of the activated area increase with stimulus duration. Functional ultrasound imaging was sensitive enough to detect hemodynamic responses evoked by only a single pulse stimulus. We also observed that the RBC velocity during activation could be separated in two distinct speed ranges with the fastest velocities located in the upper part of the cortex and slower velocities in deeper layers. For the first time, functional ultrasound imaging demonstrates its potential to image brain activity chronically in small animals and offers new insights into the spatiotemporal evolution of cerebral hemodynamics.

Synthesis of monopolar ultrasound pulses for therapy: the frequency-compounding transducer.

In diagnostic ultrasound, broadband transducers capable of short acoustic pulse emission and reception can improve axial resolution and provide sufficient bandwidth for harmonic imaging and multi-frequency excitation techniques. In histotripsy, a cavitation-based ultrasound therapy, short acoustic pulses (<2 cycles) can produce precise tissue ablation wherein lesion formation only occurs when the applied peak negative pressure exceeds an intrinsic threshold of the medium. This paper investigates a frequency compounding technique to synthesize nearly monopolar (half-cycle) ultrasound pulses. More specifically, these pulses were generated using a custom transducer composed of 23 individual relatively-broadband piezoceramic elements with various resonant frequencies (0.5, 1, 1.5, 2, and 3 MHz). Each frequency component of the transducer was capable of generating 1.5-cycle pulses with only one high-amplitude negative half-cycle using a custom 23-channel high-voltage pulser. By varying time delays of individual frequency components to allow their principal peak negative peaks to arrive at the focus of the transducer constructively, destructive interference occurs elsewhere in time and space, resulting in a monopolar pulse approximation with a dominant negative phase (with measured peak negative pressure [P-]: peak positive pressure [P+] = 4.68: 1). By inverting the excitation pulses to individual elements, monopolar pulses with a dominant positive phase can also be generated (with measured P+: P- = 4.74: 1). Experiments in RBC phantoms indicated that monopolar pulses with a dominant negative phase were able to produce very precise histotripsy-type lesions using the intrinsic threshold mechanism. Monopolar pulses with a dominant negative phase can inhibit shock scattering during histotripsy, leading to more predictable lesion formation using the intrinsic threshold mechanism, while greatly reducing any constructive interference, and potential hot-spots elsewhere. Moreover, these monopolar pulses could have many potential benefits in ultrasound imaging, including axial resolution improvement, speckle reduction, and contrast enhancement in pulse inversion imaging.

In vivo observation of the hypo-echoic "black hole" phenomenon in rat arterial bloodstream: a preliminary Study.

The "black hole," a hypo-echoic hole at the center of the bloodstream surrounded by a hyper-echoic zone in cross-sectional views, has been observed in ultrasound backscattering measurements of blood with red blood cell aggregation in in vitro studies. We investigated whether the phenomenon occurs in the in vivo arterial bloodstream of rats using a high-frequency ultrasound imaging system. Longitudinal and cross-sectional ultrasound images of the rat common carotid artery (CCA) and abdominal aorta were obtained using a 40-MHz ultrasound system. A high-frame-rate retrospective imaging mode was employed to precisely examine the dynamic changes in blood echogenicity in the arteries. When the imaging was performed with non-invasive scanning, blood echogenicity was very low in the CCA as compared with the surrounding tissues, exhibiting no hypo-echoic zone at the center of the vessel. Invasive imaging of the CCA by incising the skin and subcutaneous tissues at the imaging area provided clearer and brighter blood echo images, showing the "black hole" phenomenon near the center of the vessel in longitudinal view. The "black hole" was also observed in the abdominal aorta under direct imaging after laparotomy. The aortic "black hole" was clearly observed in both longitudinal and cross-sectional views. Although the "black hole" was always observed near the center of the arteries during the diastolic phase, it dissipated or was off-center along with the asymmetric arterial wall dilation at systole. In conclusion, we report the first in vivo observation of the hypo-echoic "black hole" caused by the radial variation of red blood cell aggregation in arterial bloodstream.

Effects of red blood cell aggregates dissociation on the estimation of ultrasound speckle image velocimetry.

Ultrasound speckle image of blood is mainly attributed by red blood cells (RBCs) which tend to form RBC aggregates. RBC aggregates are separated into individual cells when the shear force is over a certain value. The dissociation of RBC aggregates has an influence on the performance of ultrasound speckle image velocimetry (SIV) technique in which a cross-correlation algorithm is applied to the speckle images to get the velocity field information. The present study aims to investigate the effect of the dissociation of RBC aggregates on the estimation quality of SIV technique. Ultrasound B-mode images were captured from the porcine blood circulating in a mock-up flow loop with varying flow rate. To verify the measurement performance of SIV technique, the centerline velocity measured by the SIV technique was compared with that measured by Doppler spectrograms. The dissociation of RBC aggregates was estimated by using decorrelation of speckle patterns in which the subsequent window was shifted as much as the speckle displacement to compensate decorrelation caused by in-plane loss of speckle patterns. The decorrelation of speckles is considerably increased according to shear rate. Its variations are different along the radial direction. Because the dissociation of RBC aggregates changes ultrasound speckles, the estimation quality of SIV technique is significantly correlated with the decorrelation of speckles. This degradation of measurement quality may be improved by increasing the data acquisition rate. This study would be useful for simultaneous measurement of hemodynamic and hemorheological information of blood flows using only speckle images.

Pulmonary retention of primed neutrophils: a novel protective host response, which is impaired in the acute respiratory distress syndrome.

RATIONALE: Acute respiratory distress syndrome (ARDS) affects over 200000 people annually in the USA. Despite causing severe, and often refractory, hypoxaemia, the high mortality and long-term morbidity of ARDS results mainly from extra-pulmonary organ failure; however the mechanism for this organ crosstalk has not been determined. METHODS: Using autologous radiolabelled neutrophils we investigated the pulmonary transit of primed and unprimed neutrophils in humans. Flow cytometry of whole blood samples was used to assess transpulmonary neutrophil priming gradients in patients with ARDS, sepsis and perioperative controls. MAIN RESULTS: Unprimed neutrophils passed through the lungs with a transit time of 14.2 s, only 2.3 s slower than erythrocytes, and with <5% first-pass retention. Over 97% of neutrophils primed ex vivo with granulocyte macrophage colony-stimulating factor were retained on first pass, with 48% still remaining in the lungs at 40 min. Neutrophils exposed to platelet-activating factor were initially retained but subsequently released such that only 14% remained in the lungs at 40 min. Significant transpulmonary gradients of neutrophil CD62L cell surface expression were observed in ARDS compared with perioperative controls and patients with sepsis. CONCLUSIONS: We demonstrated minimal delay and retention of unprimed neutrophils transiting the healthy human pulmonary vasculature, but marked retention of primed neutrophils; these latter cells then 'deprime' and are re-released into the systemic circulation. Further, we show that this physiological depriming mechanism may fail in patients with ARDS, resulting in increased numbers of primed neutrophils within the systemic circulation. This identifies a potential mechanism for the remote organ damage observed in patients with ARDS.

Phosphoenolpyruvate carboxylase identified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism.

Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in the Plasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10(Δpepc) ), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10(Δpepc) had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using (13)C-U-D-glucose and (13)C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10(Δpepc) and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of (13)C,(15)N-U-glutamine was similar in both parasite lines, although the flux was lower in D10(Δpepc); it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery.

Synovial hemangioma of Hoffa fat pad demonstrated by RBC SPECT/CT.

Synovial hemangioma of Hoffa fat pad is an extremely rare disease, which occurs in the knee joints. Because synovial hemangioma often shows nonspecific symptoms, such as pain, swelling, limping, or limitation of motion, diagnosis could be delayed in many cases. We present a 7-year-old boy referred to our department for Tc red blood cell (RBC) scan for the confirmation of hemangioma suggested by the MRI. RBC scan demonstrated intense radioactivity accumulation in Hoffa pad of right knee joint, and subsequent excision biopsy revealed the mass as venous hemangioma.

Contemporary Oxygenator Design Relative to Hemolysis.

Hemolysis is a well-known phenomenon during cardiovascular surgery and generally attributed to cardiopulmonary bypass, particularly when using high-resistant oxygenators. This study aimed at investigating whether transoxygenator pressure drop can be considered an independent factor of hemolysis. Additionally, intraoxygenator blood distribution and shear stress were assessed. A low-resistant (LR, n = 3), a moderate-resistant (MR, n = 3), and a high-resistant (HR, n = 3) clinically used membrane oxygenator were tested in vitro using a roller pump and freshly drawn heparinized porcine blood. Flow rates were set to 2 and 4 L/min and maximum flow compliant to the oxygenator type for 1 hour each. As a control, the oxygenator was excluded from the system. Blood samples were taken every 30 minutes for plasma-free hemoglobin assay and transoxygenator pressure was measured inline. Intraoxygenator blood distribution was assessed using an ultrasound dilution technique. Despite the relatively broad spectrum of pressure drop and resultant transoxygenator pressure drops (LR: 14-41 mmHg, MR: 29-115 mmHg, HR: 77-284 mmHg, respectively), no significant association (R2 = .074, p = .22) was found with the normalized index of hemolysis. The shear stress of each oxygenator at maximum flow rate amounted to 3.0 N/m2 (LR), 5.7 N/m2 (MR), and 8.4 N/m2 (HR), respectively. Analysis of blood flow distribution curves (kurtosis and skewness) revealed intraoxygenator blood flow distribution to become more homogeneous when blood flow rates increased. Contemporary oxygenators were shown not to be a predominant factor for red blood cell damage.

Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography.

As capillaries exhibit heterogeneous and fluctuating dynamics even during baseline, a technique measuring red blood cell (RBC) speed and flux over many capillaries at the same time is needed. Here, we report that optical coherence tomography can capture individual RBC passage simultaneously over many capillaries located at different depths. Further, we demonstrate the ability to quantify RBC speed, flux, and linear density. This technique will provide a means to monitor microvascular flow dynamics over many capillaries at different depths at the same time.

The effect of flow acceleration on the cyclic variation of blood echogenicity under pulsatile flow.

It has been shown that the echogenicity of blood varies during a flow cycle under pulsatile flow both in vitro and in vivo. In general, the echogenicity of flowing whole blood increases during the early systole phase and then reduces to a minimum at late diastole. While it has been postulated that this cyclic variation is associated with the dynamics of erythrocyte aggregation, the mechanisms underlying this increasing echogenicity with flow velocity remain uncertain. The effect of flow acceleration has also been proposed as an explanation for this phenomenon, but no specific experiments have been conducted to test this hypothesis. In addition, the influence of ultrasonic attenuation on the cyclic variation of echogenicity requires clarification. In the present study, a Couette flow system was designed to simulate blood flowing with different acceleration patterns, and the flow velocity, attenuation, and backscattering coefficient were measured synchronously from 20%- and 40%-hematocrit porcine whole blood and erythrocyte suspensions using 35-MHz ultrasound transducers. The results showed ultrasonic attenuation exerted only minor effects on the echogenicity of blood under pulsatile flow conditions. Cyclic variations of echogenicity were clearly observed for whole blood with a hematocrit of 40%, but no variations were apparent for erythrocyte suspensions. The echogenicity did not appear to be enhanced when instantaneous acceleration was applied to flowing blood in any case. These findings show that flow acceleration does not promote erythrocyte aggregation, even when a higher peak velocity is applied to the blood. Comparison of the results obtained with different accelerations revealed that the cyclic variation in echogenicity observed during pulsatile blood flow may be jointly attributable to the effect of shear rate and the distribution of erythrocyte on aggregation.

Technetium-labeled erythrocyte scintigraphy in acute gastrointestinal bleeding.

PURPOSE: Optimal management of acute gastrointestinal (GI) bleeding requires accurate localization of the bleeding source. The role of technetium-labeled erythrocyte scintigraphy (tagged red blood cell (TRBC) scan) in evaluating acute GI bleeding has been controversial, though recent literature suggests that it is a reliable tool and may be used as a first-line diagnostic test. We evaluated our recent experience with and the clinical outcomes of the TRBC scan in patients presenting with acute GI bleeding. METHODS: A retrospective study of 100 consecutive TRBC scans performed between April 2006 and January 2009 was conducted. Medical records of each corresponding patient were queried for pertinent data. Twenty TRBC scans performed for occult GI bleeding or >48 h after hospital admission were excluded. RESULTS: Of the 80 TRBC scans, 29 (36%) were positive and 51 (64%) were negative for bleeding. Eight (10%) were incorrect positive (leading to five incorrect operations), 12 (15%) true positive, 9 (11%) unconfirmed positive, 17 (21%) false negative, and 34 (43%) unconfirmed negative. The cause of bleeding was confirmed in 31 cases, of which the scan result was incorrect positive in 2 (7%), true positive in 12 (39%), and false negative in 17 (55%). CONCLUSIONS: TRBC scans have low positive yield as well as high incorrect positive and high false negative rates in patients with acute GI bleeding. Further research is needed to improve scan technique, refine patient selection, and determine in what setting TRBC scanning may be more clinically useful.

Klippel-Trénaunay syndrome (KTS) evaluated with bone and labeled RBC scintigraphy.

This is a case of a 4-year-old female child with gross left lower extremity deformity detected at birth, including a giant cutaneous hemangioma from flank to foot. She was found to have no other associated abnormalities and was diagnosed with Klippel-Trénaunay syndrome. This is a rare entity and literature regarding use of radionuclide imaging techniques to evaluate this is scarce. We present here bone and red cell scans performed to evaluate whether there was osseous involvement or only soft tissue disease, which showed classic signs of this condition. Patient photographs also show the syndrome's typical appearance.

Hepatoprotective effects of pecan nut shells on ethanol-induced liver damage.

The hepatoprotective activity of the aqueous extract of the shells of pecan nut was investigated against ethanol-induced liver damage. This by-product of the food industry is popularly used to treat toxicological diseases. We evaluated the phytochemical properties of pecan shell aqueous extract (AE) and its in vitro and ex vivo antioxidant activity. The AE was found to have a high content of total polyphenols (192.4±1.9 mg GAE/g), condensed tannins (58.4±2.2 mg CE/g), and antioxidant capacity, and it inhibited Fe(2+)-induced lipid peroxidation (LP) in vitro. Rats chronically treated with ethanol (Et) had increased plasmatic transaminases (ALT, AST) and gamma glutamyl transpeptidase (GGT) levels (96%, 59.13% and 465.9%, respectively), which were effectively prevented (87; 41 and 383%) by the extract (1:40, w/v). In liver, ethanol consumption increased the LP (121%) and decreased such antioxidant defenses as glutathione (GSH) (33%) and superoxide dismutase (SOD) (47%) levels, causing genotoxicity in erythrocytes. Treatment with pecan shell AE prevented the development of LP (43%), GSH and SOD depletion (33% and 109%, respectively) and ethanol-induced erythrocyte genotoxicity. Catalase activity in the liver was unchanged by ethanol but was increased by the extract (47% and 73% in AE and AE+Et, respectively). Therefore, pecan shells may be an economic agent to treat liver diseases related to ethanol consumption.