Peripheral limitations for performance: Muscle capillarization.

Sufficient delivery of oxygen and metabolic substrates, together with removal of waste products, are key elements of muscle performance. Capillaries are the primary site for this exchange in skeletal muscle and the degree of muscle capillarization affects diffusion conditions by influencing mean transit time, capillary surface area and diffusion distance. Muscle capillarization may thus represent a limiting factor for performance. Exercise training increases the number of capillaries per muscle fiber by about 10%-20% within a few weeks in untrained subjects, whereas capillary growth progresses more slowly in well-trained endurance athletes. Studies show that capillaries are tortuous, situated along and across the length of the fibers with an arrangement related to muscle fascicles. Although direct data is lacking, it is possible that years of training not only enhances capillary density but also optimizes the positioning of capillaries, to further improve the diffusion conditions. Muscle capillarization has been shown to increase oxygen extraction during exercise in humans, but direct evidence for a causal link between increased muscle capillarization and performance is scarce. This review covers current knowledge on the implications of muscle capillarization for oxygen and glucose uptake as well as performance. A brief overview of the process of capillary growth and of physical factors, inherent to exercise, which promote angiogenesis, provides the foundation for a discussion on how different training modalities may influence muscle capillary growth. Finally, we identify three areas for future research on the role of capillarization for exercise performance.

Investigations of hypoxia-induced deoxyhemoglobin as a contrast agent for cerebral perfusion imaging.

The assessment of resting perfusion measures (mean transit time, cerebral blood flow, and cerebral blood volume) with magnetic resonance imaging currently requires the presence of a susceptibility contrast agent such as gadolinium. Here, we present an initial comparison between perfusion measures obtained using hypoxia-induced deoxyhemoglobin and gadolinium in healthy study participants. We hypothesize that resting cerebral perfusion measures obtained using precise changes of deoxyhemoglobin concentration will generate images comparable to those obtained using a clinical standard, gadolinium. Eight healthy study participants were recruited (6F; age 23-60). The study was performed using a 3-Tesla scanner with an eight-channel head coil. The experimental protocol consisted of a high-resolution T1-weighted scan followed by two BOLD sequence scans in which each participant underwent a controlled bolus of transient pulmonary hypoxia, and subsequently received an intravenous bolus of gadolinium. The resting perfusion measures calculated using hypoxia-induced deoxyhemoglobin and gadolinium yielded maps that looked spatially comparable. There was no statistical difference between methods in the average voxel-wise measures of mean transit time, relative cerebral blood flow and relative cerebral blood volume, in the gray matter or white matter within each participant. We conclude that perfusion measures generated with hypoxia-induced deoxyhemoglobin are spatially and quantitatively comparable to those generated from a gadolinium injection in the same healthy participant.

Blood Pressure Affects the Early CT Perfusion Imaging in Patients with aSAH Reflecting Early Disturbed Autoregulation.

BACKGROUND: Early computed tomography perfusion (CTP) is frequently used to predict delayed cerebral ischemia following aneurysmatic subarachnoid hemorrhage (aSAH). However, the influence of blood pressure on CTP is currently controversial (HIMALAIA trial), which differs from our clinical observations. Therefore, we aimed to investigate the influence of blood pressure on early CTP imaging in patients with aSAH. METHODS: We retrospectively analyzed the mean transit time (MTT) of early CTP imaging within 24 h after bleeding prior to aneurysm occlusion with respect to blood pressure shortly before or after the examination in 134 patients. We correlated the cerebral blood flow with the cerebral perfusion pressure in the case of patients with intracranial pressure measurement. We performed a subgroup analysis of good-grade (World Federation of Neurosurgical Societies [WFNS] I-III), poor-grade (WFNS IV-V), and solely WFNS grade V aSAH patients. RESULTS: Mean arterial pressure (MAP) significantly correlated inversely with the mean MTT in early CTP imaging (R = - 0.18, 95% confidence interval [CI] - 0.34 to - 0.01, p = 0.042). Lower mean blood pressure was significantly associated with a higher mean MTT. Subgroup analysis revealed an increasing inverse correlation when comparing WFNS I-III (R = - 0.08, 95% CI - 0.31 to 0.16, p = 0.53) patients with WFNS IV-V (R = - 0.2, 95% CI - 0.42 to 0.05, p = 0.12) patients, without reaching statistical significance. However, if only patients with WFNS V are considered, a significant and even stronger correlation between MAP and MTT (R = - 0.4, 95% CI - 0.65 to 0.07, p = 0.02) is observed. In patients with intracranial pressure monitoring, a stronger dependency of cerebral blood flow on cerebral perfusion pressure is observed for poor-grade patients compared with good-grade patients. CONCLUSIONS: The inverse correlation between MAP and MTT in early CTP imaging, increasing with the severity of aSAH, suggests an increasing disturbance of cerebral autoregulation with the severity of early brain injury. Our results emphasize the importance of maintaining physiological blood pressure values in the early phase of aSAH and preventing hypotension, especially in patients with poor-grade aSAH.

Using isotopic tracers to enhance routine watershed monitoring - Insights from an intensively managed agricultural catchment.

Experimental (research-based) and non-research-based watershed monitoring programs often differ with respect to sampling frequency, monitored variables, and monitoring objectives. Isotopic variables, which are more commonly incorporated in research-based programs, can provide an indication of water sources and the transit time of water in a catchment. These variables may be a valuable complement to traditional water quality monitoring variables and have the potential to support improved hydrologic process-related insights from long term monitoring programs that typically have low resolution sampling. The purpose of this investigation is to explore the utility of incorporating isotopic variables (specifically δ18O, δ2H, and 222Rn) into routine monthly sampling regimes by comparing insights gained from these variables to monitoring only specific conductivity and chloride. A complete annual cycle of monthly groundwater and surface water monitoring data collected from the Upper Parkhill watershed in southwestern Ontario, Canada was used to characterize baseline watershed conditions, evaluate watershed resilience to climate change, and examine contamination vulnerability. Study results provide an improved understanding of appropriate tracer use in agricultural regions with isotopic variables able to provide important insights into the seasonality of hydrologic phenomena, such as the timing of groundwater recharge. A comparison of monitoring variables to present-day hydro-meteorological conditions suggests the importance of a winter dominated hydrologic regime and the potential influence of changes in precipitation on groundwater-surface water interactions. Estimated transit time dynamics indicate the likelihood for rapid contaminant transport through surface and shallow subsurface flow and highlight the possible effects of agricultural tile drainage. The sampling approach and data analysis methods adopted in this study provide the basis for improving routine watershed monitoring programs in agricultural regions.

Evaluation of Myocardial Microcirculation in Rats under a High-Altitude Hypoxic Environment by Computed Tomography Myocardial Perfusion Imaging.

This study aims to examine the changes in myocardial microcirculation in rats in a high-altitude hypoxic environment via computed tomography (CT) myocardial perfusion imaging technology. Rats in two groups were raised in different environments from 4 weeks of age for a period of 24 weeks. At 28 weeks of age, both groups underwent CT myocardial perfusion scanning, and the following myocardial perfusion parameters were measured: time to peak (TTP), mean transit time (MTT), blood flow (BF), and blood volume (BV). Following the scan, the rats were sacrificed, the cardiac index and right ventricular hypertrophy index were obtained, and hematoxylin-eosin (HE) staining was utilized to observe the pathological changes in the myocardium. In the group of rats that are subject to a high-altitude hypoxic environment for 24 weeks (the high-altitude group), the TTP and MTT values were increased (P < 0.05), the BF and BV values were lower (P < 0.05), the right heart mass was higher (P < 0.05) than that in the low-altitude group. As shown by the pathological results of HE staining, the gap between cardiomyocytes in the high-altitude group was widened, the arrangement of cardiomyocytes was irregular, and the cells were filled with a few fat vacuoles. The myocardial microcirculation is altered in a high-altitude hypoxic environment. In particular, the myocardium is in a state of inadequate perfusion, the BF in the myocardium slows down, and the right heart displays compensatory hypertrophy.

Preoperatively estimated graft flow rate contributes to the improvement of hemodynamics in revascularization for Moyamoya disease.

OBJECTIVES: Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass operation is an effective treatment for patients with Moyamoya disease, and the hemodynamic parameters are reported to be improved after operation. However, there is no report concerning hemodynamic changes from the viewpoint of the preoperative anatomical structure of grafts. In this study, we evaluated the correlation between the preoperatively estimated blood flow of the graft obtained through image-based computational fluid dynamics (CFD) analysis and the hemodynamic changes in the acute phase after revascularization. MATERIALS AND METHODS: A total of 30 hemispheric sides of 23 patients were examined. The blood flow, that is, flow rate (FR) of the STA branches that were anastomosed to the MCA was evaluated using CFD analysis based on computed tomography (CT) angiography imaging data. The correlations between the FR and the hemodynamic changes in the acute phase after revascularization obtained through CT perfusion were assessed. RESULTS: The preoperatively estimated FR of the graft was moderately correlated with the changes in the mean transit time significantly and weakly correlated with those in the cerebral blood flow and cerebral blood volume. In addition, the FR was strongly correlated with age and the diameter of the STA from the origin to the bifurcation. CONCLUSION: The preoperatively estimated FR of the graft obtained through image-based CFD analysis contributed to the improvement of the mean transit time after revascularization. Because the FR of the graft was associated with the diameter of the STA, the size of the STA might be an important factor in postoperative hemodynamic changes. This might lead to the risk assessment of acute drastic hemodynamic changes as cerebral hyperperfusion, and consequently, better surgical outcomes might be expected.

Ischemic Tolerance Evaluated by Computed Tomography Perfusion during Balloon Test Occlusion.

OBJECTIVES: Balloon test occlusion (BTO) is performed to evaluate ischemic tolerance for large and giant cerebral aneurysms and head and neck tumors that may require parent artery occlusion. However, ischemic tolerance for the temporary test occlusion does not always guarantee a tolerance for permanent occlusion. In this study, we evaluated the utility of computed tomography (CT) perfusion during BTO to quantify ischemic tolerance for detecting delayed ischemic stroke. MATERIALS AND METHODS: Forty-one patients who underwent BTO for the internal carotid artery were included. The correlations between the parameters of CT perfusion and collateral angiographic appearance or stump pressure during BTO were evaluated. The cerebral blood flow (CBF), cerebral blood volume, mean transit time (MTT), and time to peak (TTP) were obtained through CT perfusion, and the asymmetry ratios were determined. Collateral angiographic appearances were categorized into 5 grades (0-4). RESULTS: The collateral angiographic appearance showed moderate correlations with CBF, MTT, and TTP that was significant. Of these, the absolute value of the correlation coefficient was the highest for MTT. MTT also showed a moderate correlation with stump pressure. CBF and MTT were significantly different between the poor collateral group (grades 2 and 3) and the good collateral group (grade 4). Based on the MTT, the good collateral group was identified with high sensitivity (75.0%) and specificity (81.2%). CONCLUSIONS: In BTO, the MTT obtained through CT perfusion showed a correlation with collateral angiographic appearance and stump pressure. Thus, the MTT might be useful to quantify ischemic tolerance for detecting delayed ischemic stroke.

What can we see with IVIM MRI?

Intravoxel Incoherent Motion (IVIM) refers to translational movements which within a given voxel and during the measurement time present a distribution of speeds in orientation and/or amplitude. The IVIM concept has been used to estimate perfusion in tissues as blood flow in randomly oriented capillaries mimics a pseudo-diffusion process. IVIM-based perfusion MRI, which does not require contrast agents, has gained momentum recently, especially in the field oncology. In this introductory review the basic concepts, models, technical requirements and limitations inherent to IVIM-based perfusion MRI are outlined, as well as new, non-perfusion applications of IVIM MRI, such as virtual MR Elastography.

Contemporary and emerging magnetic resonance imaging methods for evaluation of moyamoya disease.

Numerous recent technological advances offer the potential to substantially enhance the MRI evaluation of moyamoya disease (MMD). These include high-resolution volumetric imaging, high-resolution vessel wall characterization, improved cerebral angiographic and perfusion techniques, high-field imaging, fast scanning methods, and artificial intelligence. This review discusses the current state-of-the-art MRI applications in these realms, emphasizing key imaging findings, clinical utility, and areas that will benefit from further investigation. Although these techniques may apply to imaging of a wide array of neurovascular or other neurological conditions, consideration of their application to MMD is useful given the comprehensive multidimensional MRI assessment used to evaluate MMD. These MRI techniques span from basic cross-sectional to advanced functional sequences, both qualitative and quantitative.The aim of this review was to provide a comprehensive summary and analysis of current key relevant literature of advanced MRI techniques for the evaluation of MMD with image-rich case examples. These imaging methods can aid clinical characterization, help direct treatment, assist in the evaluation of treatment response, and potentially improve the understanding of the pathophysiology of MMD.

Estimation of microvascular capillary physical parameters using MRI assuming a pseudo liquid drop as model of fluid exchange on the cellular level.

AIM: One of the most important microvasculatures' geometrical variables is number of pores per capillary length that can be evaluated using MRI. The transportation of blood from inner to outer parts of the capillary is studied by the pores and the relationship among capillary wall thickness, size and the number of pores is examined. BACKGROUND: Characterization of capillary space may obtain much valuable information on the performance of tissues as well as the angiogenesis. METHODS: To estimate the number of pores, a new pseudo-liquid drop model along with appropriate quantitative physiological purposes has been investigated toward indicating a package of data on the capillary space. This model has utilized the MRI perfusion, diffusion and relaxivity parameters such as cerebral blood volume (CBV), apparent diffusion coefficient (ADC), ΔR 2 and Δ R 2 * values. To verify the model, a special protocol was designed and tested on various regions of eight male Wistar rats. RESULTS: The maximum number of pores per capillary length in the various conditions such as recovery, core, normal-recovery, and normal-core were found to be 183 ± 146, 176 ± 160, 275 ± 166, and 283 ± 143, respectively. This ratio in the normal regions was more than that of the damaged ones. The number of pores increased with increasing mean radius of the capillary and decreasing the thickness of the wall in the capillary space. CONCLUSION: Determination of the number of capillary pore may most likely help to evaluate angiogenesis in the tissues and treatment planning of abnormal ones.

Assessment of Thoracic Blood Volume by Computerized Tomography in Patients With Heart Failure and Periodic Breathing.

BACKGROUND: Periodic breathing (PB) is often observed in patients with HF at rest, with sleep and during exercise. However, mechanisms underlying abnormal ventilatory control are not entirely established. METHODS: Eleven subjects with HF (10 males, age = 69 ± 12 y) and 12 age-matched control subjects (8 males, age = 65 ± 9 y) participated in the study. PB was defined as a peak in the 0.003-0.04 Hz frequency range of the flow signal during 6 minutes of awake resting breathing. Thoracic blood volumes (Vt, thorax; Vh, heart; Vp, pulmonary), mean transit times (MTTs), and extravascular lung water (EVLW) were quantified using computerized tomography. RESULTS: PB was observed in 7 subjects with HF and was associated with worse functional status. The HF PB-present group had thoracic blood volumes nearly double those of control and HF PB-absent subjects (volumes reported as mL/m2 body surface area, P values vs control: control = 813 ± 246, HF PB-absent = 822 ± 161 P = .981, HF PB-present = 1579 ± 548 P = .002). PB was associated with longer pulmonary MTT (control = 6.7 ± 1.2 s, HF PB-absent = 6.0 ± 0.8 s, HF PB-present = 8.4 ± 1.6 s; P = .033, HF PB-present vs HF PB-absent). EVLW was not elevated in the PB group. CONCLUSIONS: Subjects with HF and PB at rest have greater centralization of blood volume.

CT Perfusion evaluation of gastric cancer: correlation with histologic type.

OBJECTIVES: To prospectively evaluate if the perfusion parameters of gastric cancer can provide information on histologic subtypes of gastric cancer. METHODS: We performed preoperative perfusion CT (PCT) and curative gastrectomy in 46 patients. PCT data were analysed using a dedicated software program. Perfusion parameters were obtained by two independent radiologists and were compared according to histologic type using Kruskal-Wallis, Mann-Whitney U test and receiver operating characteristic analysis. To assess inter-reader agreement, we used intraclass correlation coefficient (ICC). RESULTS: Inter-reader agreement for perfusion parameters was moderate to substantial (ICC = 0.585-0.678). Permeability surface value of poorly cohesive carcinoma (PCC) was significantly higher than other histologic types (47.3 ml/100 g/min in PCC vs 26.5 ml/100 g/min in non-PCC, P < 0.001). Mean transit time (MTT) of PCC was also significantly longer than non-PCC (13.0 s in PCC vs 10.3 s in non-PCC, P = 0.032). The area under the curve to predict PCC was 0.891 (P < 0.001) for permeability surface and 0.697 (P = 0.015) for MTT. CONCLUSION: Obtaining perfusion parameters from PCT was feasible in gastric cancer patients and can aid in the preoperative imaging diagnosis of PCC-type gastric cancer as the permeability surface and MTT value of PCC type gastric cancer were significantly higher than those of non-PCC. KEY POINTS: • Obtaining perfusion parameters from PCT was feasible in patients with gastric cancer. • Permeability surface and MTT were significantly higher in poorly cohesive carcinoma (PCC). • Permeability surface, MTT can aid in the preoperative imaging diagnosis of PCC.

Magnetic resonance imaging perfusion is associated with disease severity and activity in multiple sclerosis.

PURPOSE: The utility of perfusion-weighted imaging in multiple sclerosis (MS) is not well investigated. The purpose of this study was to compare baseline normalized perfusion measures in subgroups of newly diagnosed MS patients. We wanted to test the hypothesis that this method can differentiate between groups defined according to disease severity and disease activity at 1 year follow-up. METHODS: Baseline magnetic resonance imaging (MRI) including a dynamic susceptibility contrast perfusion sequence was performed on a 1.5-T scanner in 66 patients newly diagnosed with relapsing-remitting MS. From the baseline MRI, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were generated. Normalized (n) perfusion values were calculated by dividing each perfusion parameter obtained in white matter lesions by the same parameter obtained in normal-appearing white matter. Neurological examination was performed at baseline and at follow-up approximately 1 year later to establish the multiple sclerosis severity score (MSSS) and evidence of disease activity (EDA). RESULTS: Baseline normalized mean transit time (nMTT) was lower in patients with MSSS >3.79 (p = 0.016), in patients with EDA (p = 0.041), and in patients with both MSSS >3.79 and EDA (p = 0.032) at 1-year follow-up. Baseline normalized cerebral blood flow and normalized cerebral blood volume did not differ between these groups. CONCLUSION: Lower baseline nMTT was associated with higher disease severity and with presence of disease activity 1 year later in newly diagnosed MS patients. Further longitudinal studies are needed to confirm whether baseline-normalized perfusion measures can differentiate between disease severity and disease activity subgroups over time.

Disturbance of CT perfusion within 24 h after onset is associated with WFNS grade but not development of DCI in patients with aneurysmal SAH.

BACKGROUND: Delayed cerebral ischemia (DCI) is a serious complication following aneurysmal SAH (aSAH) and remains a leading cause of morbidity and mortality. We investigated whether data from CT perfusion (CTP) within 24 h after onset are associated with DCI and its outcome. METHODS: We retrospectively examined plain CT, CTP, and CT angiography (CTA) of aSAH patients on arrival. We measured the average mean transit time (aMTT) and compared it with several clinical factors, such as the age, WFNS grade, Fisher group, delayed cerebral infarction, cerebral vasospasm, and modified Rankin scale (mRS), at 1 month. Regions of interest (ROIs) were quantitatively determined in cortical and two basal ganglia areas. RESULTS: Delayed cerebral ischemia (DCI) developed in 11 patients and cerebral vasospasm in 28 patients out of a total of 86 aSAH patients scanned within 24 h after onset. The average MTT was correlated with the WFNS grade (p = 0.000), but not mRS (p = 0.128), age (p = 0.759), DCI (p = 0.669), or cerebral vasospasm (p = 0.306). On the other hand, DCI was associated with the Fisher group (p = 0.0056), mRS (p = 0.0052), and cerebral vasospasm (p = 0.000). Moreover, there were no significant differences in the average MTT within 24 h after onset between territories with and without DCI, or between patients with and without DCI. CONCLUSIONS: The current findings suggest that disturbance of CT perfusion soon after the onset is associated with the WFNS grade but not with the development of DCI. Delayed cerebral ischemia may be solely caused by cerebral vasospasm due to a clot in the cistern, but not associated with early brain injury.

Assessment of Hemodynamic Compromise Using Computed Tomography Perfusion in Combination with 123I-IMP Single-Photon Emission Computed Tomography without Acetazolamide Challenge Test.

OBJECTIVES: The acetazolamide challenge test in conjunction with 123I-IMP single-photon emission computed tomography (SPECT) is a known method of assessing cerebrovascular reserve capacity. In this study, we investigated whether CT perfusion in combination with resting state 123I-IMP SPECT could be used instead of the acetazolamide challenge test to evaluate hemodynamic compromise in patients with atherosclerotic occlusive disease. METHODS: Twenty consecutive patients with unilateral internal carotid artery or middle cerebral artery steno-occlusive disease were enrolled. 123I-IMP SPECT was performed with and without the acetazolamide challenge test, and with CT perfusion. Cerebral blood flow (CBF), cerebral blood volume, and mean transit time (MTT) obtained by CT perfusion were compared with CBF and cerebrovascular reactivity (CVR) obtained by 123I-IMP SPECT. RESULTS: The asymmetry ratio of MTT as measured by CT perfusion showed a strong correlation with the CVR to acetazolamide as measured by 123I-IMP SPECT (ρ = -.780, P <.001). Based on the CBF obtained through 123I-IMP SPECT and the MTT obtained through CT perfusion, hemodynamic compromise was detected with high sensitivity (1.000) and specificity (.929), and a cutoff value of 30% was found to be suitable for the asymmetry ratio of MTT. MTT prolongation was significantly improved after revascularization surgery in hemodynamic compromise (P = .028). CONCLUSION: MTT as measured by CT perfusion in combination with CBF as measured by resting state 123I-IMP SPECT may be useful for evaluating hemodynamic compromise as an alternative to the acetazolamide challenge test.

Carotid Artery Stenting and Blood-Brain Barrier Permeability in Subjects with Chronic Carotid Artery Stenosis.

Failure of the blood-brain barrier (BBB) is a critical event in the development and progression of diseases such as acute ischemic stroke, chronic ischemia or small vessels disease that affect the central nervous system. It is not known whether BBB breakdown in subjects with chronic carotid artery stenosis can be restrained with postoperative recovery of cerebral perfusion. The aim of the study was to assess the short-term effect of internal carotid artery stenting on basic perfusion parameters and permeability surface area-product (PS) in such a population. Forty subjects (23 males) with stenosis of >70% within a single internal carotid artery and neurological symptoms who underwent a carotid artery stenting procedure were investigated. Differences in the following computed tomography perfusion (CTP) parameters were compared before and after surgery: global cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and PS. PS acquired by CTP is used to measure the permeability of the BBB to contrast material. In all baseline cases, the CBF and CBV values were low, while MTT and TTP were high on both the ipsi- and contralateral sides compared to reference values. PS was approximately twice the normal value. CBF was higher (+6.14%), while MTT was lower (-9.34%) on the contralateral than on the ipsilateral side. All perfusion parameters improved after stenting on both the ipsilateral (CBF +22.66%; CBV +18.98%; MTT -16.09%, TTP -7.62%) and contralateral (CBF +22.27%, CBV +19.72%, MTT -14.65%, TTP -7.46%) sides. PS decreased by almost half: ipsilateral -48.11%, contralateral -45.19%. The decline in BBB permeability was symmetrical on the ipsi- and contralateral sides to the stenosis. Augmented BBB permeability can be controlled by surgical intervention in humans.

Dynamics of cerebral perfusion deficits after aneurysmal SAH - predictive value of early MTT for subsequent MTT deterioration.

BACKGROUND AND PURPOSE: The pathogenesis of poor functional outcome after aneurysmal subarachnoid hemorrhage (aSAH) is not fully understood. Microcirculatory dysfunction, which can be indirectly measured by CT perfusion (CTP), is assumed to play a central role. We evaluated the predictive value of early changes in microcirculation for secondary critical perfusion changes. MATERIALS AND METHODS: Out of 351 consecutive aSAH patients, 166 patients with ≥1 CTP within 72h of ictus (early CTP) and ≥3 CTPs in total were included in the retrospective analysis (53.2±12.4years of age). Receiver-operating-characteristic (ROC) analysis was performed to identify the mean transit time (MTT) threshold in early CTP with the highest sensitivity and specificity for predicting secondary critical perfusion changes >72h after ictus. The odds ratio was calculated and the threshold for the highest odds ratio was determined. RESULTS: Secondary critical perfusion changes were observed in 67/166 patients (40.4%). An early MTT 1.3 times the mean normal MTT could predict those changes with an odds ratio of 2.67 (sensitivity 67.2%, specificity 56.6%). Shifting the threshold to 1.26 times the mean normal MTT resulted in an odds ratio of 3.56 (sensitivity 79.1%, specificity 48.5%). CONCLUSIONS: Early MTT is predictive of secondary critical perfusion changes, which could have applications for neuromonitoring and treatment.

Relative Mean Transit Time Predicts Subsequent Stroke in Symptomatic Carotid Occlusion.

BACKGROUND: Mean transit time (MTT) measurements to assess cerebral hemodynamics are easily obtained by computed tomography and magnetic resonance imaging. We reviewed hemodynamic and clinical outcome data from the St. Louis Carotid Occlusion Study to determine if increased MTT was associated with an increased risk of stroke in patients with symptomatic complete carotid artery occlusion. METHODS: Positron emission tomography (PET) studies of cerebral blood volume-to-cerebral blood flow ratios were used to calculate MTTs. Mean ipsilateral (side of the occluded internal carotid artery)-to-contralateral ratios of MTTs in the middle cerebral artery territories were determined. MTT was tested as a predictor of stroke risk using Cox regression analysis. Receiver operating characteristic curves for stroke risk prediction were generated by varying the mean ispilateral-to-contralateral MTT ratio to identify an optimal cutpoint. RESULTS: Increased MTT ratio was associated with an increased risk of ipsilateral stroke (P < .001). The maximum combination of sensitivity (.778) and specificity (.763) was obtained at a cutpoint ratio of 1.387 or higher. Subjects with a MTT ratio of 1.387 or higher had a 29.3% 2-year risk of ipsilateral stroke compared to 4.6% for those without (P < .001). CONCLUSIONS: PET relative MTT ratio identified patients with symptomatic complete internal artery occlusion who were at high risk for subsequent ipsilateral stroke. Confirmation using measurements of relative MTT from other imaging modalities in a patient cohort receiving contemporary medical management is needed.

A bioimage informatics based reconstruction of breast tumor microvasculature with computational blood flow predictions.

Induction of tumor angiogenesis is among the hallmarks of cancer and a driver of metastatic cascade initiation. Recent advances in high-resolution imaging enable highly detailed three-dimensional geometrical representation of the whole-tumor microvascular architecture. This enormous increase in complexity of image-based data necessitates the application of informatics methods for the analysis, mining and reconstruction of these spatial graph data structures. We present a novel methodology that combines ex-vivo high-resolution micro-computed tomography imaging data with a bioimage informatics algorithm to track and reconstruct the whole-tumor vasculature of a human breast cancer model. The reconstructed tumor vascular network is used as an input of a computational model that estimates blood flow in each segment of the tumor microvascular network. This formulation involves a well-established biophysical model and an optimization algorithm that ensures mass balance and detailed monitoring of all the vessels that feed and drain blood from the tumor microvascular network. Perfusion maps for the whole-tumor microvascular network are computed. Morphological and hemodynamic indices from different regions are compared to infer their role in overall tumor perfusion.

Ischemic stroke in evolution: predictive value of perfusion computed tomography.

BACKGROUND: Various perfusion computed tomography (PCT) parameters have been used to identify tissue at risk of infarction in the setting of acute stroke. The purpose of this study was to examine predictive value of the PCT parameters commonly used in clinical practice to define ischemic penumbra. The patient selection criterion aimed to exclude the effect of thrombolysis from the imaging data. METHODS: Consecutive acute stroke patients were screened and a total of 18 patients who initially underwent PCT and CT angiogram (CTA) on presentation but did not qualify to receive thrombolytic therapy were selected. The PCT images were postprocessed using a delay-sensitive deconvolution algorithm. All the patients had follow-up noncontrast CT or magnetic resonance imaging to delineate the extent of their infarction. The extent of lesions on PCT maps calculated from mean transit time (MTT), time to peak (TTP), cerebral blood flow, and cerebral blood volume were compared and correlated with the final infarct size. A collateral grading score was used to measure collateral blood supply on the CTA studies. RESULTS: The average size of MTT lesions was larger than infarct lesions (P < .05). The correlation coefficient of TTP/infarct lesions (r = .95) was better than MTT/infarct lesions (r = .66) (P = .004). CONCLUSIONS: A widely accepted threshold to define MTT lesions overestimates the ischemic penumbra. In this setting, TTP with appropriate threshold is a better predictor of infarct in acute stroke patients. The MTT/TTP mismatch correlates with the status of collateral blood supply to the tissue at risk of infarction.