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Cerebral hypoperfusion impairs brain activity and leads to cognitive impairment. Left and right common carotid arteries (CCA) are the major source of cerebral blood supply. It remains unclear whether blood flow in both CCA contributes equally to brain activity. Here, CCA blood flow was evaluated using ultrasonography in 23 patients with cerebrovascular diseases. Resting-state brain activity and cognitive status were also assessed using magnetoencephalography and a cognitive subscale of the Functional Independence Measure, respectively, to explore the relationships between blood flow, functional brain activity, and cognitive status. Our findings indicated that there was an association between blood flow and resting-state brain activity, and between resting-state brain activity and cognitive status. However, blood flow was not significantly associated with cognitive status directly. Furthermore, blood velocity in the right CCA correlated with resting-state brain activity, but not with the resistance index. In contrast, the resistance index in the left CCA correlated with resting-state brain activity, but not with blood velocity. Our findings suggest that hypoperfusion is important in the right CCA, whereas cerebral microcirculation is important in the left CCA for brain activity. Hence, this asymmetry should be considered when designing appropriate therapeutic strategies.

Impairments in oxygen delivery and consumption can lead to reduced muscle endurance and physical disability. Perfusion, a measure of microvascular blood flow, provides information on nutrient delivery. T2* provides information about relative tissue oxygenation. Changes in these parameters following stress, such as exercise, can yield important information about imbalance between delivery and consumption. In this study, we implemented novel golden angle radial MRI acquisition technique to simultaneously quantify muscle perfusion and T2* at 7T with improved temporal resolution, and demonstrated assessment of spatial and temporal changes in these parameters within calf muscles during recovery from plantar flexion exercise. Nine healthy subjects participated the studies. At rest, perfusion and T2* in gastrocnemius muscle group within calf muscle were 5 ± 2 mL/100 g/min and 21.1 ± 3 ms respectively. Then the subjects performed plantar flexion exercise producing a torque of ~8ft-lb. Immediately after the exercise, perfusion was elevated to 79.3 ± 9 mL/100 g/min and T2* was decreased by 6 ± 3%. The time constants for 50% perfusion and T2* recovery were 54.1 ± 10 s and 68.5 ± 7 s respectively. These results demonstrate successful simultaneous quantification of perfusion and T2* in skeletal muscle using the developed technique.

Bone perfusion is an essential physiological measure reflecting vasculature status and tissue viability of the skeletal system. Arterial spin labeling (ASL), as a non-invasive and non-contrast enhanced perfusion imaging method, is an attractive approach for human research studies. To evaluate the feasibility of ASL perfusion imaging of knee bone marrow in the distal femoral condyle at a 3 T MRI scanner, a study was performed with eight healthy volunteers (three males and five females, 26 ± 2 years old) and two patients (male, 15 and 11 years old) with diagnosed stage II juvenile osteochondritis dissecans (JOCD). ASL imaging utilized a flow-sensitive alternating inversion recovery method for labeling and a single-shot fast spin echo sequence for image readout. In addition to quantitative knee bone marrow ASL imaging, studies were also performed to evaluate the effects of prolonged post-bolus delay and varied labeling size. ASL imaging was successfully performed with all volunteers. Despite the benefits of hyper-intensive signal suppression within bone marrow, the use of a prolonged post-bolus delay caused excessive perfusion signal decay, resulting in low perfusion signal-to-noise ratio (SNR) and poor image quality. Bone marrow perfusion signal changed with the labeling size, suggesting that the measured bone marrow perfusion signal is flow-associated. The means and standard deviations of bone marrow blood flow, spatial SNR, and temporal SNR from the quantitative perfusion study were 38.3 ± 5.2 mL/100 g/min, 3.31 ± 0.48, and 1.33 ± 0.31, respectively. The imaging results from JOCD patients demonstrated the potential of ASL imaging to detect disease-associated bone marrow perfusion changes. This study demonstrates that it is feasible to perform ASL imaging of knee bone marrow in the distal femoral condyle at 3 T.

An increased and more effective microvascular perfusion is postulated to play a key role in the physiological adaptation of Sherpa highlanders to the hypobaric hypoxia encountered at high altitude. To investigate this, we used Lempel-Ziv complexity (LZC) analysis to explore the spatiotemporal dynamics of the variability of the skin microvascular blood flux (BF) signals measured at the forearm and finger, in 32 lowlanders (LL) and 46 Sherpa highlanders (SH) during the Xtreme Everest 2 expedition. Measurements were made at baseline (BL) (LL: London 35 m; SH: Kathmandu 1300 m) and at Everest base camp (LL and SH: EBC 5,300 m). We found that BF signal content increased with ascent to EBC in both SH and LL. At both altitudes, LZC of the BF signals was significantly higher in SH, and was related to local slow-wave flow-motion activity over multiple spatial and temporal scales. In SH, BF LZC was also positively associated with LZC of the simultaneously measured tissue oxygenation signals. These data provide robust mechanistic information of microvascular network functionality and flexibility during hypoxic exposure on ascent to high altitude. They demonstrate the importance of a sustained heterogeneity of network perfusion, associated with local vaso-control mechanisms, to effective tissue oxygenation during hypobaric hypoxia.

Cerebral perfusion is determined by segmental perfusion pressure for the intracranial compartment (SPP), which is lower than cerebral perfusion pressure (CPP) because of extracranial stenosis. We used the Thevenin model of Starling resistors to represent the intra-extra-cranial compartments, with outflow pressures ICP and Pe, to express SPP = Pd–ICP = FFR*CPP–Ge(1 − FFR)(ICP–Pe). Here Pd is intracranial inflow pressure in the circle of Willis, ICP—intracranial pressure; FFR = Pd/Pa is fractional flow reserve (Pd scaled to the systemic pressure Pa), Ge—relative extracranial conductance. The second term (cerebral venous steal) decreases SPP when FFR Pe. We verified the SPP equation in a bench of fluid flow through the collapsible tubes. We estimated Pd, measuring pressure in the intra-extracranial collateral (supraorbital artery) in a volunteer. To manipulate extracranial outflow pressure Pe, we inflated the infraorbital cuff, which led to the Pd increase and directional Doppler flow signal reversal in the supraorbital artery. SPP equation accounts for the hemodynamic effect of inflow stenosis and intra-extracranial flow diversion, and is a more precise perfusion pressure target than CPP for the intracranial compartment. Manipulation of intra-extracranial pressure gradient ICP–Pe can augment intracranial inflow pressure (Pd) and reverse intra-extracranial steal.

The aim of this study was the assessment of the relationship between cigarette smoking and optic nerve and macular vessel density measured by optical coherence tomography angiography. We examined 30 eyes from 30 healthy habitual smokers. The examination was performed using a high-speed and high-resolution spectral-domain optical coherence tomography RTVue XR Avanti with AngioVue (Optovue, Fremont, CA, USA) with a split-spectrum amplitude-decorrelation angiography algorithm. Blood pressure, heart rate, vascular density in the area of the optic nerve head (4.5*4.5 mm) and vascular density with the foveal avascular zone in the central macula (3.0*3.0 mm) were measured and analyzed before, immediately after and 30 minutes after cigarette smoking. Quantitative measurements were carried out by AngioAnalytics Phase 7 software. Immediately after smoking both heart rate and blood pressure increased significantly (p

Moyamoya disease (MMD) is a chronic, steno-occlusive cerebrovascular disorder of unknown etiology. Surgical treatment is the only known effective method to restore blood flow to affected areas of the brain. However, there are lack of generally accepted noninvasive tools for therapeutic outcome monitoring. As dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) is the standard MR perfusion imaging technique in the clinical setting, we investigated a dataset of nineteen pediatric MMD patients with one preoperational and multiple periodic DSC MRI examinations for four to thirty-eight months after indirect revascularization. A rigid gamma variate model was used to derive two nondeconvolution-based perfusion parameters: time to peak (TTP) and full width at half maximum (FWHM) for monitoring transitional bolus delay and dispersion changes respectively. TTP and FWHM values were normalized to the cerebellum. Here, we report that 74% (14/19) of patients improve in both TTP and FWHM measurements, and whereof 57% (8/14) improve more noticeably on FWHM. TTP is in good agreement with Tmax in estimating bolus delay. Our study data also suggest bolus dispersion estimated by FWHM is an additional, informative indicator in pediatric MMD monitoring.

Quantitative measurement of lung perfusion is a promising tool to evaluate lung pathophysiology as well as to assess disease severity and monitor treatment. However, this novel technique has not been adopted clinically due to various technical and physiological challenges; and it is still in the early developmental phase where the correlation between lung pathophysiology and perfusion maps is being explored. The purpose of this research work is to quantify the impact of pulmonary artery occlusion on lung perfusion indices using lung dynamic perfusion CT (DPCT). We performed Lung DPCT in ten anesthetized, mechanically ventilated juvenile pigs (18.6–20.2 kg) with a range of reversible pulmonary artery occlusions (0%, 40–59%, 60–79%, 80–99%, and 100%) created with a balloon catheter. For each arterial occlusion, DPCT data was analyzed using first-pass kinetics to derive blood flow (BF), blood volume (BV) and mean transit time (MTT) perfusion maps. Two radiologists qualitatively assessed perfusion maps for the presence or absence of perfusion defects. Perfusion maps were also analyzed quantitatively using a linear segmented mixed model to determine the thresholds of arterial occlusion associated with perfusion derangement. Inter-observer agreement was assessed using Kappa statistics. Correlation between arterial occlusion and perfusion indices was evaluated using the Spearman-rank correlation coefficient. Our results determined that perfusion defects were detected qualitatively in BF, BV and MTT perfusion maps for occlusions larger than 55%, 80% and 55% respectively. Inter-observer agreement was very good with Kappa scores > 0.92. Quantitative analysis of the perfusion maps determined the arterial occlusion threshold for perfusion defects was 50%, 76% and 44% for BF, BV and MTT respectively. Spearman-rank correlation coefficients between arterial occlusion and normalized perfusion values were strong (− 0.92, − 0.72, and 0.78 for BF, BV and MTT, respectively) and were statically significant (p 0.01). These findings demonstrate that lung DPCT enables quantification and stratification of pulmonary artery occlusion into three categories: mild, moderate and severe. Severe (occlusion ≥ 80%) alters all perfusion indices; mild (occlusion BF and MTT but BV is preserved.

The purpose of this study was to investigate the influence of arterial input function (AIF) selection on the quantification of vertebral perfusion using axial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). In this study, axial DCE-MRI was performed on 2 vertebrae in each of eight healthy volunteers (mean age, 36.9 years; 5 men) using a 1.5-T scanner. The pharmacokinetic parameters Ktrans, ve, and vp, derived using a Tofts model on axial DCE-MRI of the lumbar vertebrae, were evaluated using various AIFs: the population-based aortic AIF (AIF_PA), a patient-specific aortic AIF (AIF_A) and a patient-specific segmental arterial AIF (AIF_SA). Additionally, peaks and delay times were changed to simulate the effects of various AIFs on the calculation of perfusion parameters. Nonparametric analyses including the Wilcoxon signed rank test and the Kruskal–Wallis test with a Dunn–Bonferroni post hoc analysis were performed. In simulation, Ktrans and ve increased as the peak in the AIF decreased, but vp increased when delay time in the AIF increased. In humans, the estimated Ktrans and ve were significantly smaller using AIF_A compared to AIF_SA no matter the computation style (pixel-wise or region-of-interest based). Both these perfusion parameters were significantly greater using AIF_SA compared to AIF_A.

To describe patterns of reperfusion in the superficial vascular plexus (SVP), deep capillary plexus (DCP) and choriocapillaris (CC) as detected on optical coherence tomography (OCTA) in cynomogulus macaque monkey model following increase in intraocular pressure by an intravitreal injection. Animal imaging study. Two cynomogulus macaque monkeys. A 100 µL intravitreal injection (IVI) of saline was given in one eye of each monkey. Serial OCTA using a Zeiss Plex Elite 9000 was used to evaluate reperfusion patterns within the SCP, DCP, and CC. OCTA evidence of perfusion. Pulsation of the central retinal artery was detected after the intraocular pressure was elevated to 98 and ≥ 99 mmHg from IVI. Episodic flow within the SVP arterioles and venules and poor visualization of flow in capillaries was noted during the initial phase of elevated pressure. As the pressure declined, the flow signal within the DCP appeared initially as dots, which progressed laterally to loops which form capillary vortex configuration. Recovery of flow within the SVP and CC appeared sooner than in the DCP. At 40 min after the injection, well after the intraocular pressure normalized, the retinal and choriocapillaris vascular perfusion showed focal defects in every layer. Compared with pre-injection images, vessel density in the DCP was 68.8% and 78.6% of baseline in monkey 1 and monkey 2, respectively. In contrast vessel density in the SVP recovered to 84.2% and 88.9% of baseline. Increases in intraocular pressure from IVI have the potential to affect every layer of blood flow in the fundus. After nominal return of intraocular pressure, focal defects in flow persisted, which may result in longer term damage to the retina.

There is a need for noninvasive repeatable biomarkers to detect early cancer treatment response and spare non-responders unnecessary morbidities and costs. Here, we introduce three-dimensional (3D) dynamic contrast enhanced ultrasound (DCE-US) perfusion map characterization as inexpensive, bedside and longitudinal indicator of tumor perfusion for prediction of vascular changes and therapy response. More specifically, we developed computational tools to generate perfusion maps in 3D of tumor blood flow, and identified repeatable quantitative features to use in machine-learning models to capture subtle multi-parametric perfusion properties, including heterogeneity. Models were developed and trained in mice data and tested in a separate mouse cohort, as well as early validation clinical data consisting of patients receiving therapy for liver metastases. Models had excellent (ROC-AUC > 0.9) prediction of response in pre-clinical data, as well as proof-of-concept clinical data. Significant correlations with histological assessments of tumor vasculature were noted (Spearman R > 0.70) in pre-clinical data. Our approach can identify responders based on early perfusion changes, using perfusion properties correlated to gold-standard vascular properties.

The physiologically important relationship between oxygen saturation and blood flow is not entirely understood, particularly with regard to the multiple velocity components of flow and temperature. While our previous studies used classic laser Doppler flowmetry combined with an enhanced perfusion probe to assess local blood flow following thermal stimulation, oxygen saturation signals were not assessed. Thus, the current study used multiscale entropy (MSE) and multiscale fuzzy entropy (MFE) to measure the complexity of oxygen saturation signals following thermal stimulation in healthy subjects. The results indicate that thermal stimulation increases oxygen saturation and affects the measured signal complexity in a temperature-dependent fashion. Furthermore, stimulus temperature not only affects the correlation between speed-resolved blood perfusion and oxygen saturation, but also the correlation between the complexity area indices (CAI) of the two signals. These results reflect the complexity of local regulation and adaptation processes in response to stimuli at different temperatures.

Optical coherence tomography angiography (OCT-A) is a non-invasive alternative to fluorescein angiography that allows for the study of the retinal and choroidal vasculatures. In this retrospective cohort study of 28 patients with retinitis pigmentosa (RP), we used OCT-A to quantify changes in perfusion density, foveal avascular zone (FAZ) area, and choriocapillaris blood flow over time and correlated these variables with ellipsoid zone (EZ) line width and best-corrected visual acuity (BCVA). Perfusion density decreased by 2.42 ± 0.62% per year at the superior capillary plexus (SCP) (P = 0.001) and 2.41 ± 0.76% per year at the deep capillary plexus (DCP) (P = 0.004). FAZ area increased by 0.078 ± 0.021 mm2 per year (P = 0.001) at the SCP and 0.152 ± 0.039 mm2 per year (P = 0.001) at the DCP. No changes were observed in the choriocapillaris blood flow. EZ line width had the strongest correlation to perfusion density at the SCP (r = 0.660 and 0.635, first and second visit, respectively, P = 0.001), while BCVA most strongly correlated with FAZ area at the SCP (r = 0.679 and 0.548, P = 0.001 and 0.003). Our results suggest that OCT-A is a useful tool for monitoring RP disease progression and may be used to measure retinal vascular parameters as outcomes in clinical trials.

In this study, we reported a new technique based on laser speckle flowgraphy to record the ocular blood flow in rabbits under deep anesthesia, and proposed parameters to characterize retinal ischemia. We applied the proposed technique to study the correlation of blood flow between the eyes of normal non-anesthetized animals, and to characterize the occlusion of the internal carotid artery (ICA) and external carotid artery (ECA). We established a correlation in blood flow between the eyes of non-anesthetized animals, and derived two new parameters, namely, the laterality index and vascular perfusion estimate (VPE). Our experimental results from 16 eyes (of 13 New Zealand white rabbits) showed a reduction in ocular blood flow with a significant decrease in the VPE after the occlusion of the ECA (p

Blood carries oxygen and nutrients to the trillions of cells in our body to sustain vital life processes. Lack of blood perfusion can cause irreversible cell damage. Therefore, blood perfusion measurement has widespread clinical applications. In this paper, we develop PulseCam — a new camera-based, motion-robust, and highly sensitive blood perfusion imaging modality with 1 mm spatial resolution and 1 frame-per-second temporal resolution. Existing camera-only blood perfusion imaging modality suffers from two core challenges: (i) motion artifact, and (ii) small signal recovery in the presence of large surface reflection and measurement noise. PulseCam addresses these challenges by robustly combining the video recording from the camera with a pulse waveform measured using a conventional pulse oximeter to obtain reliable blood perfusion maps in the presence of motion artifacts and outliers in the video recordings. For video stabilization, we adopt a novel brightness-invariant optical flow algorithm that helps us reduce error in blood perfusion estimate below 10% in different motion scenarios compared to 20–30% error when using current approaches. PulseCam can detect subtle changes in blood perfusion below the skin with at least two times better sensitivity, three times better response time, and is significantly cheaper compared to infrared thermography. PulseCam can also detect venous or partial blood flow occlusion that is difficult to identify using existing modalities such as the perfusion index measured using a pulse oximeter. With the help of a pilot clinical study, we also demonstrate that PulseCam is robust and reliable in an operationally challenging surgery room setting. We anticipate that PulseCam will be used both at the bedside as well as a point-of-care blood perfusion imaging device to visualize and analyze blood perfusion in an easy-to-use and cost-effective manner.

Although optimal therapy for myocardial infarction includes reperfusion to restore blood flow to the ischemic region, ischemia/reperfusion (IR) also initiates an inflammatory response likely contributing to adverse left ventricular (LV) extracellular matrix (ECM) remodeling. Galectin-3 (Gal-3), a β-galactoside-binding-lectin, promotes cardiac remodeling and dysfunction. Our aim is to investigate whether Gal-3 pharmacological inhibition using modified citrus pectin (MCP) improves cardiac remodeling and functional changes associated with IR. Wistar rats were treated with MCP from 1 day before until 8 days after IR (coronary artery ligation) injury. Invasive hemodynamics revealed that both LV contractility and LV compliance were impaired in IR rats. LV compliance was improved by MCP treatment 8 days after IR. Cardiac magnetic resonance imaging showed decreased LV perfusion in IR rats, which was improved with MCP. There was no difference in LV hypertrophy in MCP-treated compared to untreated IR rats. However, MCP treatment decreased the ischemic area as well as Gal-3 expression. Gal-3 blockade paralleled lower myocardial inflammation and reduced fibrosis. These novel data showing the benefits of MCP in compliance and ECM remodeling in IR reinforces previously published data showing the therapeutic potential of Gal-3 inhibition.

The purpose of this study is to evaluate the effect of haemodialysis on perfused vessel density, choroidal thickness (CT), and retinal thickness in end-stage renal disease (ESRD) using swept-source optical coherence tomography angiography (SS-OCTA). We studied twenty-nine eyes of 29 ESRD patients by ophthalmologic examination and SS-OCTA before and after haemodialysis. The colour-coded perfusion density maps were generated and perfused vessel density was calculated. Changes in systemic and other ocular parameters such as retinal and choroidal thickness were measured and analysed. Total perfused vessel density decreased significantly after haemodialysis in the choriocapillaris; it was not significantly different in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP). Total CT decreased significantly, but total retinal thickness was not significantly different. There was no significant correlation between choriocapillaris perfused vessel density and CT. The reduction in choriocapillaris perfused vessel density correlated with the decrease in systolic and mean arterial blood pressures. The decrease in CT correlated with the ultrafiltration volume. There were no significant systemic and ocular factors affecting change in retinal thickness and perfused vessel density of SCP and DCP. This is the first study to assess the effect of haemodialysis on blood flow changes using SS-OCTA; changes may be more prominent in the choroidal compared to the retinal layer.

To compare in patients with untreated rectal cancer quantitative perfusion parameters calculated from 3rd-generation dual-source dynamic volume perfusion CT (dVPCT) with 3-Tesla-MR-perfusion with regard to data variability and tumour differentiation. In MR-perfusion, plasma flow (PF), plasma volume (PV) and mean transit time (MTT) were assessed in two measurements (M1 and M2) by the same reader. In dVPCT, blood flow (BF), blood volume (BV), MTT and permeability (PERM) were assessed respectively. CT dose values were calculated. 20 patients (60 ± 13 years) were analysed. Intra-individual and intra-reader variability of duplicate MR-perfusion measurements was higher compared to duplicate dVPCT measurements. dVPCT-derived BF, BV and PERM could differentiate between tumour and normal rectal wall (significance level for M1 and M2, respectively, regarding BF: p rd-generation dual-source CT dVPCT could be included in a standard CT-staging without exceeding national dose reference values.

The purpose of this prospective, case control study was to investigate the differences in optic nerve head blood flow measured with Laser Speckle Flowgraphy (LSFG) between Caucasian patients with normal tension glaucoma and healthy subjects. It included 20 eyes from 20 Caucasian patients with diagnosis of normal tension glaucoma and 20 eyes from age- and sex-matched healthy individuals. In the glaucoma group the antiglaucomatous therapy was paused 3 weeks prior to the investigations. Measurement of optic nerve head blood flow was performed with LSFG. The mean blur rate was obtained for different vascular compartments of the optic nerve head. Parameters for the characterization of pulse-waveform of the mean blur rate were calculated. It was shown that the mean blur rate was significantly lower in the glaucoma group compared to the control group (P

This pilot study aimed to investigate the utility of near-infrared spectroscopy/indocyanine green (NIRS/ICG) for examining patients with occlusive cerebrovascular disease. Twenty-nine patients with chronic-stage atherosclerotic occlusive cerebrovascular disease were included. The patients were monitored using NIRS at the bedside. Using ICG time-intensity curves, the affected-to-unaffected side ratios were calculated for several parameters, including the maximum ICG concentration (ΔICGmax), time to peak (TTP), rise time (RT), and blood flow index (BFI = ΔICGmax/RT), and were compared to the affected-to-unaffected side ratios of the regional cerebral blood flow (rCBF) and regional oxygen extraction fraction (rOEF) obtained using positron emission tomography with 15O-labeled gas. The BFI ratio showed the best correlation with the rCBF ratio among these parameters (r = 0.618; P = 0.0004), and the RT ratio showed the best correlation with the rOEF ratio (r = 0.593; P = 0.0007). The patients were further divided into reduced rCBF or elevated rOEF groups, and the analysis revealed significant related differences. The present results advance the measurement of ICG kinetics using NIRS as a useful tool for the detection of severely impaired perfusion with reduced rCBF or elevated rOEF. This method may be applicable as a monitoring tool for patients with acute ischemic stroke.

Invasive procedure is a prerequisite for studying coronary physiology. We established the measurement of non-invasive physiological parameters including coronary blood flow (CBF), flow velocity, and microvascular resistance using coronary computed tomography angiography (CCTA). Vessel-specific CBF was derived from transluminal attenuation flow encoding (TAFE) and then tested using three separate datasets consisted of computational simulation, human perfusion CT, and human CCTA. TAFE-derived CBF correlated well with measured vessel-specific myocardial blood flow and CBF. TAFE-derived CBF per myocardial mass consistently decreased with the progressive severity of stenosis, and it was found to better to detect significant stenosis than transluminal attenuation gradient (TAG). With the addition of vessel anatomy, TAFE-derived CBF could calculate flow velocity and microvascular resistance. The results of non-invasively acquired parameters according to the severity of stenosis were similar to those obtained through invasive physiology studies. Our study demonstrated that non-invasive comprehensive coronary physiology parameters can be derived from CCTA without any pre-specified condition or performing complex heavy computational processes. Our findings are expected to expand the clinical coverage of CCTA and coronary physiology.

Blood vessels are important tissue structures that deliver oxygen and nutrition. In tumour tissue, abnormal blood vessels, which are hyperpermeable and immature, are often formed; these tissues also have irregular vascularisation and intravasation. This situation leads to hypoperfusion in tumour tissue along with low oxygen and nutrition depletion; this is also called the tumour microenvironment and is characterised by hypoxia, depleted nutrition, low pH and high interstitial pressure. This environment induces resistance to anticancer drugs, which causes an increase in anticancer drug doses, leading to increased side effects. We hypothesised that normalised tumour blood vessels would improve tumour tissue perfusion, resupply nutrition and re-oxygenate the tumour tissue. Chemotherapy would then be more effective and cause a decrease in anticancer drug doses. Here we report a neovascularisation-inducing drug that improved tumour vascular abnormalities, such as low blood flow, blood leakage and abnormal vessel structure. These results could lead to not only an increased chemo-sensitivity and tissue-drug distribution but also an up-regulated efficiency for cancer chemotherapy. This suggests that tumour blood vessel normalisation therapy accompanied by angiogenesis may be a novel strategy for cancer therapy.

The pathogenesis of chronic kidney disease (CKD) is multifactorial. In the progression of CKD arthropathy, arteriosclerosis may alter the knee subchondral bone marrow by altering blood flow through the bone vasculature. Herein, multi-parametric MRI assessment, including dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), magnetic resonance spectroscopy (MRS), MRI T2*, contrast enhanced MR angiography (CE-MRA), and micro-CT were applied in a rodent nephrectomy model to: 1) investigate the blood perfusion of subchondral bone marrow and its relationship to fat water content and trabeculation pattern in CKD and 2) demonstrate the feasibility of using multi-parametric MRI parameters as imaging biomarkers to evaluate the disease’s progression. Two groups of rats in our study underwent either 1) no intervention or 2) 5/6 nephrectomy. We found that in the CKD group, perfusion amplitude A and elimination constant k el values were significantly decreased, and vascular permeability k ep was significantly increased. MRS showed that fat fraction (FF) was significantly lower, water fraction (WF) was significantly higher in the CKD group. Micro-CT showed a significant loss of trabecular bone. Knee subchondral bone marrow perfusion deficiency in experimental CKD may be associated with decreased fat content, increased water content, and sparse trabeculation.

In this prospective study, 36 patients with stage III non-small cell lung cancers (NSCLC), who underwent dynamic contrast-enhanced MRI (DCE-MRI) before concurrent chemo-radiotherapy (CCRT) were enrolled. Pharmacokinetic analysis was carried out after non-rigid motion registration. The perfusion parameters [including Blood Flow (BF), Blood Volume (BV), Mean Transit Time (MTT)] and permeability parameters [including endothelial transfer constant (Ktrans), reflux rate (Kep), fractional extravascular extracellular space volume (Ve), fractional plasma volume (Vp)] were calculated, and their relationship with tumor regression was evaluated. The value of these parameters on predicting responders were calculated by receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis was conducted to find the independent variables. Tumor regression rate is negatively correlated with Ve and its standard variation Ve_SD and positively correlated with Ktrans and Kep. Significant differences between responders and non-responders existed in Ktrans, Kep, Ve, Ve_SD, MTT, BV_SD and MTT_SD (P e e was a significant predictor. Baseline perfusion and permeability parameters calculated from DCE-MRI were seen to be a viable tool for predicting the early treatment response after CCRT of NSCLC.

Capillaries pervade human physiology. The mean intercapillary distance is only about 100 μm in human tissue, which indicates the extent of nutrient diffusion. In engineered tissue the lack of capillaries, along with the associated perfusion, is problematic because it leads to hypoxic stress and necrosis. However, a capillary is not easy to engineer due to its complex cytoarchitecture. Here, it is shown that it is possible to create in vitro, in about 30 min, a tubular microenvironment with an elastic modulus and porosity consistent with human tissue that functionally mimicks a bona fide capillary using “live cell lithography”(LCL) to control the type and position of cells on a composite hydrogel scaffold. Furthermore, it is established that these constructs support the forces associated with blood flow and produce nutrient gradients similar to those measured in vivo. With LCL, capillaries can be constructed with single cell precision—no other method for tissue engineering offers such precision. Since the time required for assembly scales with the number of cells, this method is likely to be adapted first to create minimal functional units of human tissue that constitute organs, consisting of a heterogeneous population of 100–1000 cells, organized hierarchically to express a predictable function.

Skin malignant melanoma is a highly angiogenic cancer, necessitating early diagnosis for positive prognosis. The current diagnostic standard of biopsy and histological examination inevitably leads to many unnecessary invasive excisions. Here, we propose a non-invasive method of identification of melanoma based on blood flow dynamics. We consider a wide frequency range from 0.005–2 Hz associated with both local vascular regulation and effects of cardiac pulsation. Combining uniquely the power of oscillations associated with individual physiological processes we obtain a marker which distinguishes between melanoma and atypical nevi with sensitivity of 100% and specificity of 90.9%. The method reveals valuable functional information about the melanoma microenvironment. It also provides the means for simple, accurate, in vivo distinction between malignant melanoma and atypical nevi and may lead to a substantial reduction in the number of biopsies currently undertaken.

Thrombus formation is a multiscale phenomenon triggered by platelet deposition over a protrombotic surface (eg. a ruptured atherosclerotic plaque). Despite the medical urgency for computational tools that aid in the early diagnosis of thrombotic events, the integration of computational models of thrombus formation at different scales requires a comprehensive understanding of the role and limitation of each modelling approach. We propose three different modelling approaches to predict platelet deposition. Specifically, we consider measurements of platelet deposition under blood flow conditions in a perfusion chamber for different time periods (3, 5, 10, 20 and 30 minutes) at shear rates of 212 s−1, 1390 s−1 and 1690 s−1. Our modelling approaches are: i) a model based on the mass-transfer boundary layer theory; ii) a machine-learning approach; and iii) a phenomenological model. The results indicate that the three approaches on average have median errors of 21%, 20.7% and 14.2%, respectively. Our study demonstrates the feasibility of using an empirical data set as a proxy for a real-patient scenario in which practitioners have accumulated data on a given number of patients and want to obtain a diagnosis for a new patient about whom they only have the current observation of a certain number of variables.