Tissue Transit Time Research Articles

Urine Biomarkers Combined With Ultrasound for the Diagnosis of Obstruction in Pediatric Hydronephrosis.

Introduction: To establish the efficacy of ultrasound (US) combined with urine biomarkers in differentiating patients who require surgical management from those who do not, avoiding invasive investigations.Materials and Methods: From February 2019 to February 2021, all pediatric patients who presented with hydronephrosis were selected for the study. All renal units (RU) were evaluated by US, and fresh frozen voided urine samples were collected at the time of inclusion. Hydronephrosis grade was evaluated by the Society for Fetal Urology (SFU) and an alternative grading system (AGS). Patients who had high-grade hydronephrosis on US were referred to renal scan (RS) or intervention, when there was an increase of dilatation in subsequent follow-up images. Fresh frozen urine from the control group with no history of renal diseases and no renal anomalies on US was collected. We compared differences of US parameters combined with urine biomarkers between surgically and non-surgically managed patients and between the groups of patients when they were stratified by different RS findings and analyzed whether urinary biomarkers give any additional value to US. Instead of the anterior–posterior diameter (APD), we used its ratio with mid-parenchymal thickness. The additional efficacy of biomarkers to US was calculated when the US component was derived to a cumulative APD/mid-parenchymal ratio.Results: Sixty-four patients with hydronephrosis were prospectively included in the study accounting for a total of 81 patient visits and 162 RUs evaluated. A control group of 26 patients was collected. The mean age at inclusion in the hydronephrosis group was 43.7(±45.5) months, and a mean age in a control group was 61.2(±41.3) months. The cumulative APD/mid-parenchymal ratio combined with urinary albumin, β2 microglobulin (β2-M), and urinary neutrophil gelatinase-associated lipocalcin may have a better performance in the prediction of surgical intervention than the cumulative APD/mid-parenchymal ratio alone (p = 0.1). The best performance to detect the increased tissue transit time and obstructive curve on RS was demonstrated by the β2-M creatinine ratio. An increased cumulative APD/mid-parenchymal ratio with biomarkers together had a fairly good sensitivity and specificity for detection of DRF < 40%.Conclusions: According to our data, the APD/mid-parenchymal ratio alone has good efficacy in prediction of surgery and abnormal RS findings especially when combined with urine biomarkers.

The relationship between epicardial fat tissue thickness and transit time flow measurement values of coronary artery bypass grafts

Introduction: Epicardial fat tissue, the true visceral adipose depot of the heart, has been associated with changes in both cardiac function and morphology. This study aimed to show the relationship between epicardial fat tissue (EFT) thickness and graft flow dynamics in arterial and venous grafts in coronary artery bypass graft surgery (CABG). Methods: Patients underwent transthoracic echocardiography before surgery and epicardial fat thickness were evaluated. The patients were divided into two groups as EFT value <5.5 (group 1) mm and ≥5.5 (group 2) mm. One hundred eighty-one patients with a total of 434 grafts (162 arterial and272 venous) underwent isolated coronary artery bypass grafting surgery. All grafts were examined by transit time flow meter intraoperatively. Results: The mean epicardial fat tissue thickness values were 4.9±0.8 mm and 6.1±1.3 mm, respectively.Mean graft flow values of left internal mammary artery was 44.21±23.2 mL/min in group 1 and39.65 ± 19.2 mL/min in group 2 (P = 0.041). Similarly, mean graft flow values were higher in group1 in all venous grafts regardless of which vessel bypass was performed. There is a significant negative correlation between epicardial fat thickness and mean graft flow. Conclusion: Epicardial fat thickness measurement preoperatively might provide additional data for the faith of the graft.

Predictors of Renal Functional Improvement After Pyeloplasty in Ureteropelvic Junction Obstruction: Clinical Value of Visually Assessed Renal Tissue Tracer Transit in 99mTc-mercaptoacetyltriglycine Renography

To determine the clinical value of visually assessed renal tissue transit time (TTT) in 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renography for patients undergoing pyeloplasty. Medical records of 164 patients who underwent dismembered pyeloplasty were retrospectively reviewed. Baseline and postoperative renal ultrasonography and 99mTc-MAG3 renography were performed. Two urologists blinded to clinical data evaluated the renography and classified TTT as timely or delayed based on visualization of the tracer in the kidney pelvis between 2 and 10 minutes. Renal functional change after pyeloplasty was compared between patients in the timely and delayed groups. A total of 126 patients (median age, 9 months) were evaluated after excluding patients with bilateral ureteropelvic junction obstruction, a single functioning kidney, duplicated ureter, or <3 months of follow-up. There were no differences between 89 patients with timely TTT and 37 patients with delayed TTT in mean preoperative hydronephrosis grade (3.7 vs 3.8) and pelvic diameter (3.1 cm vs 3.4 cm). Although the pre- and postoperative mean values of differential renal function (DRF) were significantly higher in the timely group than in the delayed group (47.2% vs 38.3% and 47.9% vs 44.6%), DRF change was greater in the delayed group (6.3% vs 0.6%). In multivariate analysis, delayed TTT was the only significant predictor of >5% improvement in renal function after pyeloplasty. Delayed TTT in 99mTc-MAG3 renography was a significant predictor of renal functional improvement after pyeloplasty in ureteropelvic junction obstruction. Because substantial improvement of renal function is anticipated, we recommend immediate pyeloplasty in patients with delayed TTT and decreased DRF.

Pancreatic L-Glutamine Administration Protects Pig Islets From Cold Ischemic Injury and Increases Resistance Toward Inflammatory Mediators.

The isolation and transplantation of porcine islets represent a future option for the treatment of type 1 diabetic patients. Stringent product release criteria and limited availability of transgenic and specific pathogen-free pigs will essentially require processing of explanted pig pancreata in specialized, possibly remote isolation facilities, whereby pancreata are exposed to cold ischemia due to prolonged tissue transit time. In the present study we investigated whether pancreas oxygenation can be efficiently combined with an antioxidant strategy utilizing intraductal L-glutamine administration. Pig pancreata were intraductally perfused after retrieval and after cold storage in oxygen-precharged perfluorohexyloctane utilizing University of Wisconsin solution supplemented with (n = 16) or without (n = 14) 5 mmol/L L-glutamine. After isolation purified islets were subjected to extensive quality assessment. Islet recovery postpurification was significantly higher in glutamine-treated pancreata (77.0 ± 3.3% vs. 60.3 ± 6.0%, p < 0.05). Glutamine administration increased intraislet content of reduced glutathione (117.8 ± 16.5 vs. 15.9 ± 2.8 ng/ng protein, p < 0.001) associated with increased islet recovery after culture (65.8 ± 12.1% vs. 40.3 ± 11.7%, p < 0.05), enhanced glucose stimulation index (1.82 ± 0.16 vs. 1.38 ± 0.10, p < 0.05), and improved posttransplant function in diabetic nude mice (p < 0.05). Furthermore, intraductally administered glutamine increased pig islet resistance toward reactive oxygen species, nitric oxide, and high-dose proinflammatory cytokines. The present study demonstrates that quality and function of pig islets exposed to warm and cold ischemia can significantly be improved using intraductal l-glutamine administration. As the efficiency of the intraductal route may be inferior compared to intravascular administration further studies should aim on assessment of l-glutamine as supplement for pancreas perfusion during organ procurement.

Cerebral Tissue Transit Time in Patients with Sickle Cell Anemia

Introduction Accurate characterization of cerebral blood flow (CBF) in patients with sickle cell anemia (SCA) is imperative given the occurrence of neurovascular sequelae in this population. Arterial Spin Labeling (ASL) is a promising MRI modality that has been used to quantify CBF in SCA by several groups. Unfortunately, ASL quantification has proven challenging in SCA given the unique phenotype found in these patients including decreased hematocrit, elevated blood velocity an abnormal rheologic properties. As a result, there are conflicting accounts of ASL perfusion in this population. One of the key parameters of ASL quantification is the time between the labeling of spins in the neck and the downstream diffusion of those spins into parenchymal tissue, termed tissue transit time (TT). Delayed tissue TT is a known consequence of many neurovascular pathologies, including stroke. Given the elevated cerebral blood velocity and flow in response to anemia, however it is generally assumed that tissue TT is shorter in SCA but has yet to be studied. In order to improve ASL quantification and characterize this neurovascular biomarker we measured ASL derived tissue TT in healthy patients with SCA and ethnicity matched controls.Methods All patients were recruited with informed consent or assent and this study was approved by the Children's HospitalLos Angeles institutional review board. Exclusion criteria included pregnancy, previous stroke, acute chest, pain crisis or hospitalization within one month. All MRI scans were performed on an Achieva 3T scanner with an 8 channel head coil. Tissue TT was measured using two single shot, GRASE, ASL acquisitions, one with velocity spoiling gradients (venc 5 cm/s) and one without. Pseudo continuous ASL had a label duration of 1150ms and delay of 1500ms. Single slice phase contrast MRI of the carotids and vertebral arteries measured arterial blood velocity and global CBF. Hemoglobin level was determined on the day of the study.Results Eight patients with SCA (7 SS, 1 SC; 15.8 + 4.4yo; 5F, 3M) and nine ethnicity matched healthy controls (36.4 + 4.1yo; 6 F, 3M) were recruited. Patients with SCA had a lower hemoglobin levels (SCA, 10.1 + 0.64 g/dl, CTRL 13.7 + 0.58) and elevated CBF (SCA, 76.6 + 5.8 ml/100g/min, CTRL 49.0 + 4.4 ml/100g/min). Regional ASL perfusion asymmetries were observed in several SCA subjects. These asymmetries were not present in corresponding tissue TT maps (Figure 1). There was a trending difference in tissue TT between the two groups (SCA 1588 + 49.8, CTRL 1696 + 46.9 ms, p=.1). After multivariate analysis, sex and global CBF were the only predictors of tissue TT, r2=.54 (Figure 2).Discussion Our data is the first of our knowledge to measure the tissue TT in patients with SCA. Tissue TT is distinct from the bolus arrival time or arterial TT which corresponds to the arrival time of tracer at the imaging region. Tissue transit time is more sensitive to microvascular flow and diffusion effects and may reflect microvascular health and blood brain barrier integrity. Our measurement of tissue TT is congruent with other findings in separate neurovascular pathologies and suggests that gender and global CBF must be considered when quantifying ASL perfusion. These preliminary results also offer insight into the perfusion asymmetries observed in the ASL SCA literature. We found that perfusion asymmetries do not correlate with tissue TT suggesting either 1) tissue TT is conserved despite differences in regional flow or 2) a separate source of error is leading to spurious regional perfusion quantification, ie labeling efficiency. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Contrast-enhanced ultrasound evaluation of peripheral microcirculation in diabetic patients: effects of cigarette smoking

Cigarette smoking and diabetes mellitus predisposes to vascular disease. Our study aimed to evaluate the chronic effects of cigarette smoking on peripheral microcirculation assessed with contrast-enhanced ultrasound (CEUS) in diabetic patients. The study population comprised ten smoker (7/3 M/W, age 42-76 years) and 16 nonsmoker (8/8 men/women, age 47-80 years) diabetic patients. The ankle-brachial index (ABI) was determined, and colour Doppler ultrasound (CDUS) of the lower legs was performed to determine the presence of peripheral arteriopathy disease (PAD). Microvascular blood flow in the gastrocnemius muscle was evaluated with CEUS. No differences were observed in ABI and CDUS examination between smokers and nonsmokers. Smoking had a significant effect on microcirculatory function. Timeto-peak (TTP), arrival time in tissue (ATt) and artery/ tissue transit time (A/Ttt) were significantly prolonged in smokers (TTP 43.76 ± 9.38 s vs. 34.12 ± 6.8 s, p=0.011, ATt 28.9 ± 7.5s vs. 22.4 ± 6.4 s, p=0.017 and A/Ttt 6.81 ± 4.52 s vs. 3.25 ± 3.27 s, p=0.02), with no significant differences between patients with and without PAD. The long-term exposure to cigarette smoke affects microcirculatory function. Contrast imaging is a noninvasive technique that can document these effects.

Functional CT in lung with a conventional scanner: simulations and sampling considerations

Due to rapid transit times, motion artefacts from breathing and the low signal intensity, functional computed tomography (f-CT) studies in lung tissue remain challenging with conventional CT scanners. The purpose of this study is to examine the accuracy of parameter estimates when performing deconvolution analysis with signals from lung tissue. The effects of partial volume averaging in lung tissue, differing transit times, variable vascular and capillary responses, expected noise levels, differing sampling rate and durations were simulated on a computer. Deconvolution using singular-value decomposition (SVD) analysis was performed for realistic lung signals using published and measured values of the arterial input and noise levels. The accuracy, bias and variance of the estimated residue functions and their associated parameter estimates were evaluated. We find that f-CT signals may be measured and analysed using SVD and other deconvolution approaches. Functional CT signals in the lung may be analysed provided that the rise and fall of the tissue and input curves are well sampled (regardless of sampling rate) and noise levels in the lung ROI tissue are approximately 20 HU or less, even for regions of interest that are mostly occupied by air. Estimates of the mean tissue transit time (MTT) are insensitive to air volume. Other decovolution methods such as fast Fourier transform methods provide more accurate estimates of PBF, whereas SVD approaches provide more accurate estimates of pulmonary blood volume and MTT. F-CT of the lung with a conventional scanner should be possible, when the extra dose is not a consideration.

Arterial transit time imaging with flow encoding arterial spin tagging (FEAST).

Arterial spin labeling (ASL) perfusion imaging provides direct and absolute measurement of cerebral blood flow (CBF). Arterial transit time is a related physiological parameter reflecting the duration for the labeled spins to reach the brain region of interest. Most of the existing ASL approaches to assess arterial transit time rely on multiple measurements at various postlabeling delay times, and thus are vulnerable to motion artifact as well as computational error. We describe the use of flow encoding arterial spin tagging (FEAST) technique to measure tissue transit time, which can be derived from the ratio between the ASL signals measured with and without appropriate bipolar gradients. In the present study, we provided a theoretical framework and carried out an experimental validation during steady-state imaging. The global mean tissue transit time was approximately 1100 and 1400 ms for two conditions of bipolar gradients with specific encoding velocity (Venc) of 29 and 8 mm/sec, respectively. The mean tissue transit time measured within cerebral vascular territories was shortest in the deep middle cerebral artery (MCA) territory. Application of the FEAST technique in two patients with cerebrovascular disease demonstrated prolonged tissue transit times in the affected vascular territories which were consistent with results from other MR imaging modalities.

Effect of plasma cholesterol on red blood cell oxygen transport.

1. Oxygen (O2) transfer from the blood to tissues is a function of the red blood cell (RBC) O2 saturation (SO2), the plasma O2 content being negligible. Under conditions of increased tissue O2 demand, the SO2 of arterial blood does not change appreciably (97%); however, the SO2 of mixed venous blood, equal to that of the perfused tissues, can go as low as 20%. 2. Tissue O2 availability is limited by the exposure time to a RBC, which decreases under conditions of maximum stress (< 1 s). If the O2 unloading time was to increase significantly, because of a decrease in the RBC diffusion constant or an increase in the RBC membrane thickness, the RBC O2 unloading time would exceed tissue (e.g. cardiac) transit time and O2 transfer would be impaired. 3. Cholesterol constitutes the non-polar, hydrophobic lipid of the enveloping layer of the RBC membrane. As the cholesterol content of the RBC increases, the fluidity of the membrane decreases and the lipid shell stiffens. 4. Early studies demonstrated that high blood cholesterol concentrations were associated with reduced blood O2 transport; in essence, the haemoglobin dissociation curve was shifted to the left. 5. Current investigations have shown that the cholesterol RBC membrane barrier to O2 diffusion delayed O2 entry into the RBC during saturation and delayed O2 release from the RBC during desaturation. In an analysis of 93 patients divided by their cholesterol concentration into five groups, the percentage change in blood O2 diffusion was inversely proportional to the cholesterol concentration. 6. The RBC membrane cholesterol is in equilibrium with the plasma cholesterol concentration. It stands to reason that as the plasma cholesterol increases, the RBC membrane becomes impaired and O2 transport is reduced. 7. The implications of this new perspective on O2 transport include the ability to increase tissue oxygenation by lowering plasma cholesterol.

Hyperacute stroke: simultaneous measurement of relative cerebral blood volume, relative cerebral blood flow, and mean tissue transit time.

To investigate additional information provided by maps of relative cerebral blood flow in functional magnetic resonance (MR) imaging of human hyperacute cerebral ischemic stroke. Diffusion-weighted and hemodynamic MR imaging were performed in 23 patients less than 12 hours after the onset of symptoms. Maps of relative cerebral blood flow and tracer mean tissue transit time were computed, as were maps of apparent diffusion and relative cerebral blood volume. Acute lesion volumes on the maps were compared with follow-up imaging findings. In 15 of 23 subjects (65%), blood flow maps revealed hemodynamic abnormalities not visible on blood volume maps. A mismatch between initial blood flow and diffusion findings predicted growth of infarct more often (12 of 15 subjects with infarcts that grew) than did a mismatch between initial blood volume and diffusion findings (eight of 15). However, lesion volumes on blood volume and diffusion maps correlated better with eventual infarct volumes (r > 0.90) than did those on blood flow and tracer mean transit time maps (r approximately 0.6), likely as a result of threshold effects. In eight patients, blood volume was elevated around the diffusion abnormality, suggesting a compensatory hemodynamic response. MR imaging can delineate areas of altered blood flow, blood volume, and water mobility in hyperacute human stroke. Predictive models of tissue outcome may benefit by including computation of both relative cerebral blood flow and blood volume.

Zerebrovaskuläre Erkrankungen

Aim of this study was to develop a method for the calculation and display of regional cerebral blood flow (rCBF) in ml/100 g brain tissue/min, regional cerebral blood volume (rCBV) in ml/100 g brain tissue and mean transit time (MTT) in seconds by applying datasets of bolus-tracking MRI. During a bolus injection of 0.1 mmol/kg Gadolinium-DTPA a series of transversal T2*-weighted images was recorded. A special software has been developed to calculate the relative concentration of contrast medium and fit a synthetic curve on a voxel basis. For each voxel rCBF, rCBV and MTT could be derived from a combination of the fit parameters and displayed in a parameter map. The values of rCBV and rCBF of patients without cerebrovascular disease corresponded well with PET results from literature. In 9 patients with cerebrovascular disease the calculated hemodynamic parameters correlated with the results of brain-SPECT and stable Xenon-CT. This technique may be used for quantitative measurement and mapping of brain perfusion. Especially in patients with cerebrovascular disease this method can provide additional information for prognosis and therapy.

Functional, physiological, and metabolic toolbox for clinical magnetic resonance imaging: Integration of acquisition and analysis strategies

Selected neuroimaging strategies have been integrated into a clinical brain imaging protocol to provide quantitative high-resolution functional, physiological, and metabolic maps to complement exquisitely detailed anatomic images without excessively prolonging the conventional clinical examination or analysis time. The physiological maps of blood pool parameters (relative cerebral blood volume, tissue transit time, and arrival time), apparent diffusion coefficient, tissue water content, and functional neuronal activation maps are derived from series of images acquired with echo-planar imaging. The metabolic map reflecting tissue sodium homeostasis (tissue sodium concentration) is acquired using twisted projection imaging and a customized dual-tuned, dual-quadrature 23Na/1H brain radiofrequency coil that ensures coregistration of data and avoids moving the patient. The different types of acquired images are transferred to a common file format with customized file management software and the corresponding maps are derived by applying appropriate fitting algorithms. Customized software allows rapid interrogation and manipulation of all resultant images and maps for detailed but rapid interpretation, printing, and archiving immediately following completion of acquisition. As all acquisitions and processing are performed by the magnetic resonance technologist, the neuroradiologist is able to focus on the interpretation of this immensely rich data set. © 1997 John Wiley & Sons, Inc. Int J Imaging Syst Technol, 8, 572–581, 1997

Malignant uveal melanoma and similar lesions studied by computed tomography.

Forty-four patients with intraocular disease were studied by computed tomography (CT); in 19 cases malignant uveal melanoma was considered the likely diagnosis. CT proved to be accurate in determining the location and size of uveal melanomas, demonstrating scleral invasion, and differentiating melanoma from choroidal detachment or angioma, toxocariasis, and senile macular degeneration. Astrocytic retinal hamartoma and medulloepithelioma could not be distinguished from melanoma with CT. On CT, uveal melanomas appeared as hyperdense lesions with slight to moderate contrast enhancement. Tumors thinner than 2 mm could not be seen. Using dynamic CT, we noted moderate peak amplitude, normal or delayed tissue transit time, and persistently elevated washout phase (downslope), indicating increased permeability as the result of an impaired tumor blood barrier. Histological types of uveal melanoma could not be differentiated on the basis of circulatory patterns. Dynamic CT may be useful in distinguishing uveal melanoma from choroidal hemangioma or hematoma.

Observations on the Myelocyte to Tissue Transit Time (MTT) in Acute Leukaemia and Other Proliferative Disorders

SummaryThe myelocyte to tissue transit time (MTT) was determined by labelling leucocytes in vivo with radioactive diisopropylfluorophosphate (DF32P) and determining the time for labelled leucocytes to disappear from the blood. Normally this is complete in 22 days or less. Prolongation of MTT suggests that the later stages of granulopoiesis may be impaired (dysgranulopoiesis). Dysgranulo‐poiesis was found previously in patients with acute myelogenous and myelo‐monocytic leukaemia. In this study we have found that MTT was reduced during treatment of the acute leukaemia with cy to toxic drugs, suggesting that there was a defect in myelocyte maturation in this disease. In addition we have found evidence of dysgranulopoiesis in patients (a) whose acute leukaemia was in complete remission, (b) with myeloproliferative disorders, and (c) with obscure blood dyscrasias without leukaemia. These findings suggest that acute leukaemia may be antedated by a proliferative disorder more frequently than is usually apparent, and that remission of acute leukaemia does not necessarily depend upon marrow repopulation by normal cell lines.