Mean Transit Time Research Articles

P482 Diagnostic accuracy of contrast-enhanced ultrasound for fibrotic strictures of Crohn’s disease: a systematic review and meta-analysis of individual participant data

Abstract Background Crohn's disease (CD) often leads to the development of intestinal strictures, requiring effective differentiation between inflammatory and fibrotic for the optimal treatment strategies. Despite recent advances in drug development targeting fibrosis, current evaluation methods remain insufficient. Contrast-enhanced ultrasound (CEUS) is a promising modality for assessing vascularity and inflammation, yet its accuracy in fibrosis detection needs more validation. Methods A systematic review and meta-analysis were conducted using IPD to determine the diagnostic accuracy of CEUS in identifying intestinal fibrosis in CD. Our search included databases such as MEDLINE, EMBASE, and Web of Science up until March 23, 2023. Inclusion criteria required a confirmed diagnosis of CD and studies that evaluated the accuracy of CEUS parameters, including total area under the curve (AUC), wash-in AUC, wash-out AUC, peak enhancement, wash-in perfusion index, wash-in rate, wash-out rate, rise time, fall time, and mean transit time related to fibrosis in CD (Figure 1 (A)). The quality of included studies was assessed using the QUADAS-2 tool, with each study mandatorily using surgical specimen pathology as a reference standard in at least one instance. Results Our qualitative synthesis included eight studies encompassing 306 patients. These studies were generally assessed to have a high risk of bias. It is important to note that while peak enhancement and AUC were frequently examined across studies, neither parameter had established absolute cutoff values for the diagnosis of fibrosis. From the three studies where IPD was available, detailed data from 80 patients were included in the meta-analysis (colon n=11 and small bowel n= 69). Among them, 54 underwent surgical intervention with fibrosis being confirmed in 31. The highest diagnostic accuracy was observed for total AUC and wash-in AUC, with pooled sensitivity and specificity for predicting fibrosis at 0.86 (95% CI, 0.59–0.97) and 0.25 (95% CI, 0.03–0.76), respectively (Figure 1 (B)). Conclusion This meta-analysis with IPD pioneers the exclusive evaluation of CEUS for fibrotic strictures in CD. It reveals a significant risk of bias in the primary research and a notable absence of consensus on the CEUS parameters' threshold values for distinguishing fibrosis from inflammation. The observed low specificity highlights the need for innovative strategies in future research, such as integrating CEUS with techniques like elastography, to enhance the precision of fibrosis detection in CD. PROSPERO 2020 CRD42020214472. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020214472

Usefulness of intratumoral perfusion analysis for assessing biological features of non-functional pancreatic neuroendocrine neoplasm.

Here, we evaluated the usefulness of intratumoral perfusion analysis using preoperative contrast-enhanced CT (E-CT) to assess biological features of non-functional pancreatic neuroendocrine neoplasms (NF-PanNENs). We retrospectively studied 44 patients who underwent curative surgery for NF-PanNENs. We used preoperative E-CT with compartment model analysis to calculate the tumor perfusion parameters K1 (inflow rate constant), 1/k2 (mean transit time), and K1/k2 (distribution volume). We assessed the association between perfusion parameters and biological features of NF-PanNENs, including the WHO classification tumor histopathological grade and prognosis after surgery. Patients in this study had a neuroendocrine tumor (NET) G1 (n = 32) or NET G2 (n = 12). Neither NET G3 or NEC tumors were observed. Among perfusion parameters, K1 was the most accurate predictor of the high-grade tumor (AUC: 0.726). K1-low (< 0.028 s-1) was significantly associated with large tumors (≥ 20 mm) (p = 0.022), high mitotic index (p = 0.017), high Ki-67 index (p = 0.004), and lymphatic invasion (p = 0.025). Synchronous extra-pancreatic metastasis, including lymph node metastasis or liver metastasis, more frequently developed in K1-low patients than in K1-high patients (29% vs 4%, p = 0.025). Disease-free survival of patients with a K1-low tumor was poorer than that of patients with a K1-high tumor (p = 0.005). Furthermore, no patient with a K1-high tumor developed recurrence after initial surgery. The perfusion parameters obtained using E-CT were significantly associated with biological features and prognosis of NF-PanNENs.

Clinical value of ultrasound parameters PI, TTP, and MTT in assessing cervical lymph node metastasis of papillary thyroid carcinoma.

To determine the clinical value of ultrasound in assessing cervical lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC). The medical records of 179 PTC patients treated in Shandong Provincial Qianfoshan Hospital between March 2016 and March 2019 were collected. The patients were assigned to a transfer group (54 cases) and a non-transfer group (125 cases) according to their pathologic results. The ultrasound parameters (peak intensity (PI), time to peak (TTP), and mean transit time (MTT)) of the two groups were compared. Then, multivariate logistic regression was used to analysis the results, and receiver operating characteristic (ROC) curves were plotted to evaluate the value of risk factors in predicting CLNM. The transfer group showed notably lower PI, TTP and MTT than the non-transfer group (P<0.001), and focus diameter, microcalcification, multiple foci, PI, TTP, and MTT were identified as independent risk factors for LNM in patients (P<0.05). According to the ROC curve, the areas under the curves (AUCs) of microcalcification, multiple foci, and PI were all smaller than 0.7; the AUCs of focus diameter and MTT were smaller than 0.8, and the AUC of TTP was 0.855. PI, TTP, and MTT all decrease in PTC patients with CLNM, and TTP has a strong predictor for CLNM in them, with an AUC of 0.855.

Predictive Value of CT Perfusion Parameters in Traumatic Brain Injury Patients: A Longitudinal Study

Introduction: Traumatic Brain Injury (TBI) is the most common cause of mortality and morbidity worldwide. Moreover, cerebral contusions, Subdural Haemorrhages (SDH), Extradural Haemorrhages (EDH), and Subarachnoid Haemorrhage (SAH), which are secondary injuries that occur due to alterations in cerebral haemodynamics, remain unevaluated and unchecked by plain non contrast scans. Timely delineation of the cerebral perfusion status of the patient can assist in modifying treatment plans and could lead to a better recovery of the patient. Aim: To assess the cerebral haemodynamics of patients with TBI at admission and evaluate the predictive value of Computed Tomography (CT) perfusion. Materials and Methods: The present prospective longitudinal study was conducted in the Department of Radiodiagnosis and Neurosurgery, Jawaharlal Nehru Medical College and Hospital (JNMCH), Aligarh Muslim University (AMU), Aligarh, Uttar Pradesh, India, from September 2019 to September 2020. A total of 40 participants were included in the study using a purposive sampling method. CT Perfusion (CTP) was performed within 72 hours of head injury, followed by Glasgow Outcome at Discharge Scale (GODS) assessments at discharge and one month later. Cerebral perfusion parameters such as Cerebral Blood Flow (CBF), Cerebral Blood Volume (CBV), Mean Transit Time (MTT), and Time To Peak (TTP) were measured, and correlations were established using Spearman’s rank correlation coefficients to determine the relationship of GODS with CTP parameters. Results: The mean age of study subjects was 35.8±13.4 years, with a median (25th-75th percentile) of 32 (25-42.75). Among a total of 40 patients, 22 (55%) were males and 18 (45%) were females. Significant positive correlations were observed between GODS at discharge and CBF (mL/100 gm/min) at presentation, CBV (mL/100 gm/min) at presentation, and the number of normal/hyperemic territories, with correlation coefficients of 0.398, 0.329, and 0.504, respectively. A significant negative correlation was found between GODS at discharge and TTP (seconds) at presentation, with a correlation coefficient of -0.392. Similarly, significant positive correlations were observed between GODS at one month with CBF (mL/100 gm/min) at presentation and the number of normal/ hyperemic territories, with correlation coefficients of 0.407 and 0.827, respectively. A significant negative correlation was seen between GODS at one month and MTT (seconds) at presentation, with a correlation coefficient of -0.344. CBV (mL/100 gm/min) at presentation exhibited a sensitivity of 100%, followed by MTT (seconds) at presentation (71.43%), and CBF (mL/100 gm/min) at presentation (57.14%). Conversely, CBF (mL/100 gm/min) at presentation showed a specificity of 92.31%, followed by TTP (seconds) at presentation (92.31%), and CBV (mL/100 gm/min) at presentation (53.85%). In predicting unfavourable outcomes, MTT (seconds) at presentation had the lowest specificity of 7.69%. Conclusion: Perfusion CT provides additional information compared to Non Contrast Computed Tomography (NCCT) with insights into the pericontusional areas. Therefore, it can be a potential tool in the evaluation of TBI. Perfusion parameters have prognostic value, and thus, this modality should be studied with a larger sample size for more precise results.

Correlation of oxidative stress and vascular endothelial dysfunction with hippocampal perfusion in atrial fibrillation patients with cognitive impairment.

To evaluate the correlation of oxidative stress and vascular endothelial dysfunction with hippocampal perfusion in patients with atrial fibrillation and cognitive impairment. In total, 41 atrial fibrillation patients with cognitive impairment were compared to 45 atrial fibrillation patients without cognitive impairment. Oxidative stress, vascular endothelial dysfunction, hippocampal perfusion, and cognitive function were measured. Serum level of oxidized low-density lipoprotein was significantly higher in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. Serum levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were significantly higher, and nitric oxide was lower, in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. The regional cerebral blood volume, mean transit time, and time to peak were significantly higher in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. Moreover, regional cerebral blood flow was significantly lower in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. Age, left atrial diameter, and regional cerebral blood volume were negatively correlated with the cognitive function score in the atrial fibrillation + cognitive impairment group. Serum levels of oxidized low-density lipoprotein, regional cerebral blood volume, regional cerebral blood flow, mean transit time, and time to peak were significantly correlated with cognitive impairment in atrial fibrillation patients after multivariate logistic regression analysis. Hippocampal perfusion and oxidative stress were significantly correlated with cognitive impairment in atrial fibrillation patients.

Association between enlarged perivascular spaces in basal ganglia and cerebral perfusion in elderly people.

Enlarged perivascular spaces in basal ganglia (BG-EPVS) are considered an imaging marker of cerebral small vessel disease (CSVD), but its pathogenesis and pathophysiological process remain unclear. While decreased cerebral perfusion is linked to other CSVD markers, the relationship between BG-EPVS and cerebral perfusion remains ambiguous. This study aimed to explore this association. Elderly individuals with severe BG-EPVS (n = 77) and age/sex-matched controls (n = 89) underwent head CT perfusion imaging. The cerebral perfusion parameters including mean transit time (MTT), time to maximum (TMAX), cerebral blood flow (CBF), and cerebral blood volume (CBV) were quantitatively measured by symmetric regions of interest plotted in the basal ganglia region. Point-biserial correlation and logistics regression analysis were performed to investigate the association between BG-EPVS and cerebral perfusion. There were no significant differences in MTT, TMAX, or CBF between BG-EPVS group and control group. CBV was significantly lower in the BG-EPVS group (p = 0.035). Point-biserial correlation analysis showed a negative correlation between BG-EPVS and CBV (r = -0.198, p = 0.011). BG-EPVS group and control group as the dependent variable, binary logistics regression analysis showed that CBV was not an independent risk factor for severe BG-EPVS (p = 0.448). All enrolled patients were divided into four groups according to the interquartile interval of CBV. The ordered logistic regression analysis showed severe BG-EPVS was an independent risk factor for decreased CBV after adjusting for confounding factors (OR = 2.142, 95%CI: 1.211-3.788, p = 0.009). Severe BG-EPVS is an independent risk factor for decreased CBV in the elderly, however, the formation of BG-EPVS is not solely dependent on changes in CBV in this region. This finding provides information about the pathophysiological consequence caused by severe BG-EPVS.

Assessment of renal quality with quantitative contrast-enhanced ultrasound (CEUS) for differentiating kidney histopathology before procurement.

Purpose: This study aimed to investigate the use of contrast-enhanced ultrasonography (CEUS) to assess the kidneys' quality before procurement. Methods: This prospective study included 74 donors and 148 recipients of kidneys. 119 kidneys underwent quantitative analysis. Before organ procurement, potential kidney donors underwent CEUS, though organ procurement involved a zero-point puncture biopsy. CEUS parameters of the renal cortex and medulla were evaluated, including rise time (RT), time to peak (TTP), the area under the curve (AUC), wash-in slope (WIS), peak intensity (PI), and mean transit time (MTT). Donors' kidneys were classified based on their pathological. Additionally, short-term clinical indicators of renal recipients were collected and analyzed to determine whether the patients had delayed recovery of renal allograft function. Results: This experiment included 148 cases of kidney information, divided into two groups based on the Remuzzi score of the kidneys. However, 29 kidneys were excluded from the quantitative analysis due to loss or low quality of CEUS images. Comparing the time-intensity curve (TIC) of renal cortical region of interest (ROI), we found that the group with lower pathological scores exhibited higher PI (P=0.002), AUC(P=0.003), and WIS (P=0.009). TIC comparison results for renal medulla ROI revealed that the group with lower pathological scores had higher PI (P=0.010), AUC (P=0.023), and WIS (P=0.024). Conclusions: This study highlighted the potential of CEUS as a non-invasive, safe, and real-time examination method that correlates with the Remuzzi score and renal pathology. Therefore, it can be used as a prospective preoperative non-invasive evaluation method for the donor's kidney.

The differential diagnosis of lung precursor glandular lesions, micro-invasive adenocarcinoma, and invasive adenocarcinoma using low dose spectral computed tomography perfusion imaging.

Few studies about the association between computed tomography (CT) perfusion imaging parameters and invasiveness in lung adenocarcinoma (LUAD) have been conducted using low dose spectral CT perfusion imaging. The purpose of this study was to investigate application of spectral revolution CT low-dose perfusion imaging in the differential diagnosis of different pathological subtypes of LUAD. This was a cross-sectional study based on historical data from January 2018 to May 2019 in Peking University Cancer Hospital & Institute. A total of 62 cases were enrolled, including 2 cases of atypical adenomatous hyperplasia (AAH), 3 cases of adenocarcinoma in situ (AIS), 4 cases of minimally invasive adenocarcinoma (MIA), and 53 cases of invasive adenocarcinoma (IAC), all confirmed with pathology. The inclusion and exclusion criteria were regulated. Using Revolution low-dose CT perfusion imaging (GE, USA), the CT perfusion parameters of hemodynamics were obtained: blood flow (BF), blood volume (BV), impulse residue function time of arrival (IRF TO), maximum slope of increase (MSI), mean transit time (MTT), permeability surface area product (PS), positive enhancement integral (PEI), and maximum enhancement time (Tmax). Univariate analysis of variance (ANOVA) or Kruskal-Wallis test was used to compare the differences of CT perfusion quantitative parameters among AAH, AIS, MIA, and IAC. Mann-Whitney test was used to compare the difference of CT perfusion imaging parameters between preinvasive lesions (AAH and AIS) and invasive lung cancer (MIA and IAC). Statistically significant differences in IRF TO were observed in LUAD with different invasiveness, namely, among AIS, MIA, and IAC groups (0.56±0.74 vs. 0.54±1.08 vs. 4.39±2.19, P=0.004). Statistically significant differences in IRF TO were also observed between pre-invasive lesions group (AAH and AIS) and invasive lung cancer group (MIA and IAC) (1.12±1.27 vs. 3.75±2.79, P=0.031), and between AAH + AIS + MIA groups and IAC group (0.83±1.13 vs. 4.12±2.69, P<0.001). There were no statistically significant differences in other CT perfusion parameters of hemodynamics among different pathological subtypes of LUAD (P>0.05). The low-dose perfusion parameter IRF TO of revolution CT has the potential to be employed in the differential diagnosis of different pathological subtypes of LUAD.

Treatment response assessment to chemotherapy with bevacizumab for colorectal liver metastasis by contrast-enhanced ultrasound.

Though contrast-enhanced ultrasound (CEUS) perfusion parameters have been approved to be potential indicators for response to chemotherapy in solid tumors, their ability in assessment of colorectal liver metastasis (CRLM) to chemotherapy with bevacizumab (Bev) has rarely been investigated. From March 2021 to May 2022, 115 consecutive CRLM patients with CEUS pre- and post-2 months' chemotherapy with Bev were prospectively enrolled. One target lesion per patient underwent CEUS quantitative analysis with SonoLiver software. Rise time, time-to-peak, mean transit time, maximal intensity (IMAX), and area under the time-intensity curve (AUC) were assessed with region of interest (ROI) selected on whole lesion, lesion periphery, and internal lesion, respectively. The reduction and ratio of post- to pre-treatment in parameters were investigated in development cohort (n=89) and validated in internal validation cohort (n=26) according to the chronological order. With modified Response Evaluation Criteria in Solid Tumor as reference, 48, 14 responders and 41, 12 non-responders were included in development and validation cohort, respectively. Significantly smaller values of IMAX and AUC on ROIwhole, ROIperipheral, and ROIinternal, were observed post-treatment in development cohort (all P<0.05). In predicting treatment response, the influence of ROI selection was observed when using ∆IMAX and ∆AUC, while no influence was observed using ratios. Areas under the receiver operating characteristic curve (AUROCs) for ∆IMAX and ∆AUC on ROIperipheral were 0.939 (0.867-0.979), 0.951 (0.883-0.985), and 0.917 (0.740-0.988), 0.923 (0.748-0.990) in development and validation cohort, respectively. For ratios of IMAX and AUC, AUROCs were 0.976 (0.919-0.997), 0.938 (0.865-0.978), and 0.899 (0.717-0.982), 0.982 (0.836-1.000) in development and validation cohort, respectively. IMAX and AUC showed significant reductions in responders, and different analyses ROIs influence the performance of ∆IMAX and ∆AUC in response assessment. Parameters derived from ROI peripheral exhibited the most promising results in predicting treatment response.

Neurocognitive outcome post cranioplasty: The role of cerebral hemodynamics and cerebrospinal fluid dynamics.

Cranioplasty has been useful in treating the symptoms associated with the "Sunken skin flap syndrome" post decompressive craniectomy, for which various mechanisms have been proposed. In this study, we aim to assess the changes in the cerebral blood flow and intracranial cerebrospinal fluid (CSF) dynamics post cranioplasty and correlate with the improvement in the neurocognitive status. Computed tomography perfusion and cine magnetic resonance imaging studies were done to study the changes in cerebral perfusion and CSF flow dynamics postcranioplasty. The cognitive status was assessed using Montreal cognitive assessment, mini-mental state examination, and frontal assessment battery scores in the preoperative period and at 1 and 6 months follow-up. There was a significant change in cognitive status postcranioplasty, both at 1 and 6 months follow-up, which was associated with a significant improvement in cerebral blood flow, decreased mean transit time, and improvement in the mean and peak CSF flow velocities at the foramen of Magendie and aqueduct of Sylvius. Cranioplasty leads to a marked improvement in cerebral hemodynamics, which is more significant on the ipsilateral side. It also leads to increased CSF turnover and improved CSF circulation. Improved cerebral perfusion and, more importantly, CSF dynamics may be responsible for the demonstrable improvement in the neurocognition in the postcranioplasty period.

Multiparametric Analysis Combining DSC-MR Perfusion and [18F]FET-PET is Superior to aSingle Parameter Approach for Differentiation of Progressive Glioma from Radiation Necrosis.

Perfusion-weighted (PWI) magnetic resonance imaging (MRI) and O‑(2-[18F]fluoroethyl-)-l-tyrosine ([18F]FET) positron emission tomography (PET) are both useful for discrimination of progressive disease (PD) from radiation necrosis (RN) in patients with gliomas. Previous literature showed that the combined use of FET-PET and MRI-PWI is advantageous; hhowever the increased diagnostic performances were only modest compared to the use of asingle modality. Hence, the goal of this study was to further explore the benefit of combining MRI-PWI and [18F]FET-PET for differentiation of PD from RN. Secondarily, we evaluated the usefulness of cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TTP) as previous studies mainly examined cerebral blood volume (CBV). In this single center study, we retrospectively identified patients with WHO gradesII-IV gliomas with suspected tumor recurrence, presenting with ambiguous findings on structural MRI. For differentiation of PD from RN we used both MRI-PWI and [18F]FET-PET. Dynamic susceptibility contrast MRI-PWI provided normalized parameters derived from perfusion maps (r(relative)CBV, rCBF, rMTT, rTTP). Static [18F]FET-PET parameters including mean and maximum tumor to brain ratios (TBRmean, TBRmax) were calculated. Based on histopathology and radioclinical follow-up we diagnosed PD in 27and RN in 10cases. Using the receiver operating characteristic (ROC) analysis, area under the curve (AUC) values were calculated for single and multiparametric models. The performances of single and multiparametric approaches were assessed with analysis of variance and cross-validation. After application of inclusion and exclusion criteria, we included 37patients in this study. Regarding the in-sample based approach, in single parameter analysis rTBRmean (AUC = 0.91, p < 0.001), rTBRmax (AUC = 0.89, p < 0.001), rTTP (AUC = 0.87, p < 0.001) and rCBVmean (AUC = 0.84, p < 0.001) were efficacious for discrimination of PD from RN. The rCBFmean and rMTT did not reach statistical significance. Aclassification model consisting of TBRmean, rCBVmean and rTTP achieved an AUC of 0.98 (p < 0.001), outperforming the use of rTBRmean alone, which was the single parametric approach with the highest AUC. Analysis of variance confirmed the superiority of the multiparametric approach over the single parameter one (p = 0.002). While cross-validation attributed the highest AUC value to the model consisting of TBRmean and rCBVmean, it also suggested that the addition of rTTP resulted in the highest accuracy. Overall, multiparametric models performed better than single parameter ones. Amultiparametric MRI-PWI and [18F]FET-PET model consisting of TBRmean, rCBVmean and PWI rTTP significantly outperformed the use of rTBRmean alone, which was the best single parameter approach. Secondarily, we firstly report the potential usefulness of PWI rTTP for discrimination of PD from RN in patients with glioma; however, for validation of our findings the prospective studies with larger patient samples are necessary.

The age and sources of stream water in a boreal forest watershed in the permafrost region: a case study of a watershed in northeast China

Determining the age and sources of stream water is critical for understanding the watershed hydrological processes and biogeochemical cycle. In this study, daily isotope data of rainfall and runoff, as well as continuously monitored conductivity data from June to October in 2019 in-Laoyeling(LYL) watershed located in permafrost region of northeastern China were used to separate streamflow components through the application of two independent methods: isotope-based hydrograph separations (IHS) and the conductivity mass balance (CMB) methods. The results showed that stream water in a boreal forest watershed with permafrost of the Daxing’an Mountains is mainly composed of pre-event water. Although the IHS method is more sensitive and provides more details than the CMB method, the results of both methods show a similar trend. The average value of the young water fractions (Fyw) for those aged less than 65 days is 5.6%, while the mean transit time (MTT) was calculated to be 3.33 years. These findings enhance our understanding of the fundamental characteristics of runoff generation mechanisms and changes in runoff components in permafrost regions. Such knowledge is crucial for effective regional water resource management under the context of climate change, such as construction of water conservancy facilities and prediction of flood and drought disasters.

Improving the impact of different input arteries on cerebral CT perfusion parameters and ischemic penumbra

This study aims to examine the impact of different input arteries on cerebral perfusion parameters and the volume of core infarction, ischemic area, and penumbra automatically measured by software in post-processing 256-slice CT brain perfusion images. Retrospective analysis was conducted on brain perfusion images of 58 patients who underwent 256-slice multidetector CT examination for cerebral infarction. Various input arteries, including bilateral internal carotid artery (ICA), bilateral middle cerebral artery (MCA), anterior cerebral artery (ACA), and basilar artery (BA), were selected for image processing and measurements. The volumes of core infarction, ischemic area, and penumbra were automatically calculated using software. Additionally, manual measurements were per-formed by experienced doctors. Perfusion parameters including cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP) were evaluated. The change of input artery resulted in a significant difference in CBF and MTT in the penumbra and normal brain tissue areas. However, no significant difference was observed in CBV, TTP, and perfusion parameters in the core infarct area. The volumes of core infarction acquired from different input arteries showed no significant difference. Nonetheless, significant differences were found in the volume of the ischemic area and the mismatched area. The selection of different input arteries affects CT cerebral perfusion parameter values and the automatic measurement of the ischemic area and penumbra by software. Thus, when performing post-processing of CT cerebral perfusion images, it is advisable to choose the thicker internal carotid artery on the healthy side as the input artery.

A dynamic time-to-event model for prediction of acute graft-versus-host disease in patients after allogeneic hematopoietic stem cell transplantation.

Acute graft-versus-host disease (aGvHD) is a major cause of death for patients following allogeneic hematopoietic stem cell transplantation (HSCT). Effective management of moderate to severe aGvHD remains challenging despite recent advances in HSCT, emphasizing the importance of prophylaxis and risk factor identification. In this study, we analyzed data from 1479 adults who underwent HSCT between 2005 and 2017 to investigate the effects of aGvHD prophylaxis and time-dependent risk factors on the development of grades II-IV aGvHD within 100 days post-HSCT. Using a dynamic longitudinal time-to-event model, we observed a non-monotonic baseline hazard overtime with a low hazard during the first few days and a maximum hazard at day 17, described by Bateman function with a mean transit time of approximately 11 days. Multivariable analysis revealed significant time-dependent effects of white blood cell counts and cyclosporine A exposure as well as static effects of female donors for male recipients, patients with matched related donors, conditioning regimen consisting of fludarabine plus total body irradiation, and patient age in recipients of grafts from related donors on the risk to develop grades II-IV aGvHD. Additionally, we found that higher cumulative hazard on day 7 after allo-HSCT are associated with an increased incidence of grades II-IV aGvHD within 100 days indicating that an individual assessment of the cumulative hazard on day 7 could potentially serve as valuable predictor for later grades II-IV aGvHD development. Using the final model, stochastic simulations were performed to explore covariate effects on the cumulative incidence over time and to estimate risk ratios. Overall, the presented model showed good descriptive and predictive performance and provides valuable insights into the interplay of multiple static and time-dependent risk factors for the prediction of aGvHD.

Thrombolysis in Myocardial Infarction Frame Count for Coronary Blood Flow Evaluation during Interventional Diagnostic Procedures.

Background and Objectives: An interventional diagnostic procedure (IDP), including intracoronary acetylcholine (ACh) provocation and coronary physiological testing, is recommended as an invasive diagnostic standard for patients suspected of ischemia with no obstructive coronary arteries (INOCA). Recent guidelines suggest Thrombolysis In Myocardial Infarction frame count (TFC) as an alternative to wire-based coronary physiological indices for diagnosing coronary microvascular dysfunction. We evaluated trajectories of TFC during IDP and the impact of ACh provocation on TFC. Materials and Methods: This was a single-center, retrospective study. Patients who underwent IDP to diagnose INOCA were included and divided into two groups according to the positive or negative ACh provocation test. Wire-based invasive physiological assessment was preceded by ACh provocation tests and intracoronary isosorbide dinitrate (ISDN). We evaluated TFC at three different time points during IDP; pre-ACh, post-ISDN, and post-hyperemia. Results: Of 104 patients, 58 (55.8%) had positive ACh provocation test. In the positive ACh group, resting mean transit time (Tmn) and baseline resistance index were significantly higher than in the negative ACh group. Post-ISDN TFC was significantly correlated with resting Tmn (r = 0.31, p = 0.002). Absolute TFC values were highest at pre-ACh, followed by post-ISDN and post-hyperemia in both groups. All between-time point differences in TFC were statistically significant in both groups, except for the change from pre-ACh to post-ISDN in the positive ACh group. Conclusions: In patients suspected of INOCA, TFC was modestly correlated with Tmn, a surrogate of coronary blood flow. The positive ACh provocation test influenced coronary blood flow assessment during IDP.

Blood-brain Barrier Permeability May Influence Vasopressor Effects in Anesthetized Patients With Brain Tumor: An Analysis of Magnetic Resonance Imaging Data

Objective: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. We hypothesized that vasopressors induce microcirculatory flow changes, characterized by increased capillary transit time heterogeneity (CTH) and decreased mean transit time (MTT), in brain regions exhibiting BBB leakage. Methods: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. Postvasopressor to prevasopressor ratios of CTH, MTT, relative transit time heterogeneity (RTH), cerebral blood flow (CBF), cerebral blood volume, and oxygen extraction fraction (OEF) were calculated in tumor, peritumoral, hippocampal, and contralateral grey matter regions. Comparisons were made between brain regions and vasopressors. Results: During phenylephrine infusion, ratios of CTH, RTH, and CBF were greater, and ratios of MTT and OEF were lower, in the tumor region with contrast leakage compared with corresponding contralateral grey matter ratios. During ephedrine infusion, ratios of CTH, MTT, RTH, CBF, and cerebral blood volume were higher in the tumor region with leakage compared with contralateral grey matter ratios. In addition, the ratio of CBF was higher in all regions, the ratio of RTH was lower in the leaking tumor region, and the ratio of OEF was lower in peritumoral, hippocampal, and grey matter regions with ephedrine compared with phenylephrine. Conclusions: Vasopressors can induce distinct microcirculatory flow alterations in regions with compromised brain tumor barrier or BBB. Ephedrine, a combined α and β-adrenergic agonist, appears to result in fewer flow alterations and less impact on tissue oxygenation compared with phenylephrine, a pure α-adrenergic agonist.

Quantitative perfusion and water transport time model from multi b-value diffusion magnetic resonance imaging validated against neutron capture microspheres.

Quantification of perfusion in ml/100 g/min, rather than comparing relative values side-to-side, is critical at the clinical and research levels for large longitudinal and multi-center trials. Intravoxel incoherent motion (IVIM) is a non-contrast magnetic resonance imaging diffusion-based scan that uses a multitude of -values to measure various speeds of molecular perfusion and diffusion, sidestepping inaccuracy of arterial input functions or bolus kinetics. Questions remain as to the original of the signal and whether IVIM returns quantitative and accurate perfusion in a pathology setting. This study tests a novel method of IVIM perfusion quantification compared with neutron capture microspheres. We derive an expression for the quantification of capillary blood flow in ml/100 g/min by solving the three-dimensional Gaussian probability distribution and defining water transport time (WTT) as when 50% of the original water remains in the tissue of interest. Calculations were verified in a six-subject pre-clinical canine model of normocapnia, induced hypercapnia, and middle cerebral artery occlusion (ischemic stroke) and compared with quantitative microsphere perfusion. Linear regression analysis of IVIM and microsphere perfusion showed agreement (slope = 0.55, intercept = 52.5, ) with a Bland-Altman mean difference of . Linear regression between dynamic susceptibility contrast mean transit time and IVIM WTT asymmetry in infarcted tissue was excellent (, intercept = 0.3, ). Strong linear agreement was found between IVIM and reference standard infarct volume (slope = 1.01, ). The simulation of cerebrospinal fluid (CSF) suppression via inversion recovery returned a blood signal reduced by 82% from combined T1 and T2 effects. The accuracy and sensitivity of IVIM provides evidence that observed signal changes reflect cytotoxic edema and tissue perfusion and can be quantified with WTT. Partial volume contamination of CSF may be better removed during post-processing rather than with inversion recovery.

Mean transit time of water bodies in a typical soil-plant-atmosphere continuum of the subtropical monsoon region

The mean transit time (MTT) is a good indicator of water cycle processes. We know little about the MTT of different water bodies within the soil-plant-atmosphere continuum (SPAC) in the subtropical monsoon region. We estimated the MTT of stratified soil water at different depths as well as the xylem water and leaf water in typical Cinnamomum camphora woodland located in Changsha City from March 2017 to October 2019. The main methods used in this study included the stable isotope technology, the linear mixed model and the sine wave fitting method. The results showed that the stable isotopes were more depleted in summer and enriched in winter for different water bodies within the SPAC. The δ2H values of soil water gradually decreased as depth increased. The δ2H values of xylem water closely resembled those of soil water, but the δ2H values of leaf water were more positive and exhibited larger variation. Results of the linear mixed model indicated that the lower MTT values of soil water and plant water occurred between June and September, while the higher values were often observed around January and from April to May. The precipitation replenishment exhibited a significant negative correlation with the MTT. The MTT of soil water generally increased with depth, although preferential flow could enhance the replenishment of deeper soil water and subsequently reduce the MTT. The mean MTT values of xylem water and leaf water were similar. Results of the sine wave fitting method showed that the young water fraction (Fyw) of soil water gradually decreased as depth increased, while the MTT of soil water gradually increased as depth increased. The Fyw and MTT of xylem water were lower and higher than those of leaf water, respectively. Both the mean MTT values of soil water based on the linear mixed model or the sine wave fitting method increased from the surface to the deeper soil layers. The former exhibited a smaller variation range and the latter showed a larger variation range. The mean MTT value of xylem water based on the linear mixed model was 2.4 days less than that of leaf water, while the MTT value of xylem water in the sine wave fitting method was 87.4 days higher than that of leaf water. These differences may be due to the parameterization of "new/young water", the uncertainty of results, and the effect of evaporative fractionation. This study contributes to a better understanding of water transport and consumption processes within the SPAC and provides valuable insights for agricultural production and water resources management in the subtropical monsoon region.

Cerebral perfusion is elevated in a novel model of aged hAβKI APOE4 mice

AbstractBackgroundThe Model Organism Development and Evaluation for Late‐Onset Alzheimer’s Disease (MODEL‐AD) Consortium is developing the next generation of Alzheimer’s disease (AD) models based on human genomic and imaging data. Recently, MODEL‐AD has generated a new human Aβ Knock‐In (hAβKI) mouse carrying the APOE4 allele. APOE4 carriers are at increased risk for AD. Previous studies have demonstrated altered cerebrovascular integrity and function. We examined the cerebrovascular function in the hAβKI APOE4 mice at 18mo of age using perfusion‐weighted magnetic resonance imaging (PWI). We investigated brain‐wide perfusion alterations in conjunction with histopathological vessel painting.MethodsContrast‐enhanced PWI MRI (9.4T) was undertaken from hAβKI APOE4 (n = 6) and WT (n = 5) mice at 18mo of age following tail vein cannulation for Gadolinium infusion. Imaging sequences included: T1‐pre and post‐infusion, PWI (10min) and susceptibility‐weighted imaging (SWI) for blood extravasation and iron content. All data were processed using JIM v9 software for maps of cerebral blood flow (CBF), volumes (CBV), time to peak, mean transit time and dynamic susceptibility measures for blood‐brain barrier dysfunction. Manual regions of interest (ROI) were performed for cortex, temporal lobe cortex, dorsal hippocampus and thalamus, and semi‐automatic 30+ regions based on the Allen mouse brain atlas. At the end of the in vivo experiments all mice underwent vessel painting followed by microscopic analyses.ResultsCompared to WT mice at 18mo of age, hAβKI APOE4 mice exhibited elevated CBF in virtually all regions examined. CBF was elevated approx. 16%, 11%, 4% and 23% in the cortex, hippocampus, thalamus and temporal lobe cortex, respectively. CBF was significantly elevated in the retrosplenial and temporal lobe cortices (p&lt;0.05). CBV was also significantly increased in temporal lobe. Ongoing analyses will correlate vascular network measures (density, junctions, length) to PWI metrics as well as to hAβKI only mice.ConclusionsThe 18mo hAβKI APOE4 mouse compared to WT exhibited consistent brain‐wide elevations in cerebrovascular measures. This increase may represent a compensatory mechanism to maintain decreased metabolism that occurs with aging. The MODEL‐AD consortium (UCI/IUSM/JAX) continues to develop new and novel AD mouse models. All data will be made available to AD researchers via the Sage Knowledge Network (https://adknowledgeportal.synapse.org/).

Cerebral perfusion is elevated in a novel model of aged hAβKI APOE4 mice

AbstractBackgroundThe Model Organism Development and Evaluation for Late‐Onset Alzheimer’s Disease (MODEL‐AD) Consortium is developing the next generation of Alzheimer’s disease (AD) models based on human genomic and imaging data. Recently, MODEL‐AD has generated a new human Aß Knock‐In (hAßKI) mouse carrying the APOE4 allele. APOE4 carriers are at increased risk for AD. Previous studies have demonstrated altered cerebrovascular integrity and function. We examined the cerebrovascular function in the hAßKI APOE4 mice at 18mo of age using perfusion‐weighted magnetic resonance imaging (PWI). We investigated brain‐wide perfusion alterations in conjunction with histopathological vessel painting.MethodContrast‐enhanced PWI MRI (9.4T) was undertaken from hAßKI APOE4 (n = 6) and WT (n = 5) mice at 18mo of age following tail vein cannulation for Gadolinium infusion. Imaging sequences included: T1‐pre and post‐infusion, PWI (10min) and susceptibility‐weighted imaging (SWI) for blood extravasation and iron content. All data were processed using JIM v9 software for maps of cerebral blood flow (CBF), volumes (CBV), time to peak, mean transit time and dynamic susceptibility measures for blood‐brain barrier dysfunction. Manual regions of interest (ROI) were performed for cortex, temporal lobe cortex, dorsal hippocampus and thalamus, and semi‐automatic 30+ regions based on the Allen mouse brain atlas. At the end of the in vivo experiments all mice underwent vessel painting followed by microscopic analyses.ResultCompared to WT mice at 18mo of age, hAßKI APOE4 mice exhibited elevated CBF in virtually all regions examined. CBF was elevated approx. 16%, 11%, 4% and 23% in the cortex, hippocampus, thalamus and temporal lobe cortex, respectively. CBF was significantly elevated in the retrosplenial and temporal lobe cortices (p&lt;0.05). CBV was also significantly increased in temporal lobe. Ongoing analyses will correlate vascular network measures (density, junctions, length) to PWI metrics as well as to hAßKI only mice.ConclusionThe 18mo hAßKI APOE4 mouse compared to WT exhibited consistent brain‐wide elevations in cerebrovascular measures. This increase may represent a compensatory mechanism to maintain decreased metabolism that occurs with aging. The MODEL‐AD consortium (UCI/IUSM/JAX) continues to develop new and novel AD mouse models. All data will be made available to AD researchers via the Sage Knowledge Network (https://adknowledgeportal.synapse.org/).