Blood Flow Maps Research Articles

Assessment of Tumor Vascularization in Pancreatic Adenocarcinoma Using 128-Slice Perfusion Computed Tomography Imaging

Computed tomography (CT) perfusion studies can provide valuable information regarding tumor vascularization. We report on a study assessing CT perfusion characteristics in the normal pancreas and in patients with pancreatic adenocarcinoma. Twenty healthy subjects and 20 patients with histologically confirmed pancreatic adenocarcinoma were included in the study after written informed consent and approval by our institutional review board. All subjects underwent perfusion CT imaging of the pancreas using 128-slice dual-source CT. The scanning sequence included 18 scans. Parametric maps of blood volume (BV), blood flow (BF), and permeability surface area product (PS) were generated and compared with density measurements. In normal pancreas, no significant difference in perfusion values was observed between head, body, and tail of the pancreas. Mean organ values were 76.76 (SD, 15.6) mL/100 g/min, 15.80 (SD, 2.40) mL/100 g, and 27.74 (SD, 16.8) mL/100 g/min for BF, BV, and PS, respectively. Compared with the normal pancreas, a 60% reduction in BF and BV was observed in the tumor tissue. Perfusion values gradually increased toward the tumor rim. Necrotic tumor areas were identified in 25% of patients. No significant differences were observed when comparing normal pancreas and healthy pancreatic tissue in adenocarcinoma patients. The feasibility of whole-tumor perfusion imaging using 128-slice CT was demonstrated in patients with pancreatic adenocarcinoma. Perfusion CT provides additional information compared with image assessment based on density measurements (Hounsfield units) and allows noninvasive assessment of vascularization in the tumor tissue.

Principal-component-analysis-based estimation of blood flow velocities using optical coherence tomography intensity signals

The intensity signal in optical coherence tomography contains information about the translational velocity of scatterers, and can be used to quantify blood flow. We apply principal component analysis to efficiently extract this information. We also study use of nonuniform temporal sampling of the intensity signal to increase the range of quantifiable flow velocities. We demonstrate this technique in simulation, phantom and in vivo blood flow measurements, and highlight its potential to enable three-dimensional wide-field mapping of blood flow using OCT.

Early time points perfusion imaging: relative time of arrival, maximum derivatives and fractional derivatives.

Time of arrival (TOA) of a bolus of contrast agent to the tissue voxel is a reference time point critical for the Early Time Points Perfusion Imaging Method (ET) to make relative cerebral blood flow (rCBF) maps. Due to the low contrast to noise (CNR) condition at TOA, other useful reference time points known as relative time of arrival data points (rTOA) are investigated. Candidate rTOA's include the time to reach the maximum derivative, the maximum second derivative, and the maximum fractional derivative. Each rTOA retains the same relative time distance from TOA for all tissue flow levels provided that ET's basic assumption is met, namely, no contrast agent has a chance to leave the tissue before the time of rTOA. The ET's framework insures that rCBF estimates by different orders of the derivative are theoretically equivalent to each other and monkey perfusion imaging results supported the theory. In rCBF estimation, maximum values of higher order fractional derivatives may be used to replace the maximum derivative which runs a higher risk of violating ET's assumption. Using the maximum values of the derivative of orders ranging from 1 to 1.5 to 2, estimated rCBF results were found to demonstrate a gray-white matter ratio of approximately 3, a number consistent with flow ratio reported in the literature.

Deconvolution with simple extrapolation for improved cerebral blood flow measurement in dynamic susceptibility contrast magnetic resonance imaging during acute ischemic stroke

Magnetic resonance (MR) perfusion imaging is a clinical technique for measuring brain blood flow parameters during stroke and other ischemic events. Ischemia in brain tissue can be difficult to accurately measure or visualize when using MR-derived cerebral blood flow (CBF) maps. The deconvolution techniques used to estimate flow can introduce a mean transit time-dependent bias following application of noise stabilization techniques. The underestimation of the CBF values, greatest in normal tissues, causes a decrease in the image contrast observed in CBF maps between normally perfused and ischemic tissues; resulting in ischemic areas becoming less conspicuous. Through application of the proposed simple extrapolation technique, CBF biases are reduced when missing high-frequency signal components in the MR data removed during deconvolution noise stabilization are restored. The extrapolation approach was compared with other methods and showed a statistically significant increase in image contrast in CBF maps between normal and ischemic tissues for white matter ( P<.05) and performed better than most other methods for gray matter. Receiver operator characteristic curve analysis demonstrated that extrapolated CBF maps better-detected penumbral regions. Extrapolated CBF maps provided more accurate CBF estimates in simulations, suggesting that the approach may provide a better prediction of outcome in the absence of treatment.

CT Cerebral Blood Flow Maps Optimally Correlate With Admission Diffusion-Weighted Imaging in Acute Stroke but Thresholds Vary by Postprocessing Platform

Admission infarct core lesion size is an important determinant of management and outcome in acute (<9 hours) stroke. Our purposes were to: (1) determine the optimal CT perfusion parameter to define infarct core using various postprocessing platforms; and (2) establish the degree of variability in threshold values between these different platforms. We evaluated 48 consecutive cases with vessel occlusion and admission CT perfusion and diffusion-weighted imaging within 3 hours of each other. CT perfusion was acquired with a "second-generation" 66-second biphasic cine protocol and postprocessed using "standard" (from 2 vendors, "A-std" and "B-std") and "delay-corrected" (from 1 vendor, "A-dc") commercial software. Receiver operating characteristic curve analysis was performed comparing each CT perfusion parameter-both absolute and normalized to the contralateral uninvolved hemisphere-between infarcted and noninfarcted regions as defined by coregistered diffusion-weighted imaging. Cerebral blood flow had the highest accuracy (receiver operating characteristic area under the curve) for all 3 platforms (P<0.01). The maximal areas under the curve for each parameter were: absolute cerebral blood flow 0.88, cerebral blood volume 0.81, and mean transit time 0.82 and relative Cerebral blood flow 0.88, cerebral blood volume 0.83, and mean transit time 0.82. Optimal receiver operating characteristic operating point thresholds varied significantly between different platforms (Friedman test, P<0.01). Admission absolute and normalized "second-generation" cine acquired CT cerebral blood flow lesion volumes correlate more closely with diffusion-weighted imaging-defined infarct core than do those of CT cerebral blood volume or mean transit time. Although limited availability of diffusion-weighted imaging for some patients creates impetus to develop alternative methods of estimating core, the marked variability in quantification among different postprocessing software limits generalizability of parameter map thresholds between platforms.

Crossed cerebellar diaschisis after stroke: Can perfusion-weighted MRI show functional inactivation?

In this study, we aimed to assess the detection of crossed cerebellar diaschisis (CCD) following stroke by perfusion-weighted magnetic resonance imaging (PW-MRI) in comparison with positron emission tomography (PET). Both PW-MRI and 15O-water-PET were performed in acute and subacute hemispheric stroke patients. The degree of CCD was defined by regions of interest placed in the cerebellar hemispheres ipsilateral (I) and contralateral (C) to the supratentorial lesion. An asymmetry index (AI=C/I) was calculated for PET-cerebral blood flow (CBF) and MRI-based maps of CBF, cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP). The resulting AI values were compared by Bland-Altman (BA) plots and receiver operating characteristic analysis to detect the degree and presence of CCD. A total of 26 imaging procedures were performed (median age 57 years, 20/26 imaged within 48 hours after stroke). In BA plots, all four PW-MRI maps could not reliably reflect the degree of CCD. In receiver operating characteristic analysis for detection of CCD, PW-CBF performed poorly (accuracy 0.61), whereas CBV, MTT, and TTP failed (accuracy <0.60). On the basis of our findings, PW-MRI at 1.5 T is not suited to depict CCD after stroke.

Three-dimensional whole-brain perfused blood volume imaging with multimodal CT for evaluation of acute ischaemic stroke

To determine the diagnostic value of integrating three-dimensional perfused blood volume (3D PBV) with multimodal computed tomography (CT) [non-enhanced CT (NECT), CT perfusion (CTP), and CT angiography (CTA)] in acute ischaemic stroke. NECT, CTP, and CTA were performed in 25 acute ischaemic stroke patients. The ischaemia detection rate of 3D PBV was compared with the results of baseline NECT and CTP. The correlation of ischaemic lesion volume between 3D PBV, CTP images, and follow-up NECT were analysed. NECT demonstrated ischaemic signs in 12 of 25 patients with proven infarction. CTP maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and time to peak (TTP) all demonstrated perfusion deficits in 21 of 25 patients. However, 3D PBV demonstrated perfusion deficits in all of the 25 patients. Among the 25 patients, a strong correlation was found between PBV and the follow-up NECT infarct (r = 0.858). The correlation between CTP and the follow-up NECT infarct as following: CBF (r = 0.718), CBV (r = 0.785), and TTP (r = 0.569). In 14 thrombolytic patients, strong correlation was found between the ischaemic volume on 3D PBV and follow-up NECT (r = 0.798). In acute stroke patients, the combination of 3D PBV and multimodal CT (NECT, CTP, and CTA) can improve the detection rate of ischaemia and enable assessment of the full extent of ischaemia, which correlates well with follow-up NECT.

Imaging of blood flow using hyperpolarized [13C]Urea in preclinical cancer models

To demonstrate dynamic imaging of a diffusible perfusion tracer, hyperpolarized [(13)C]urea, for regional measurement of blood flow in preclinical cancer models. A pulse sequence using balanced steady state free precession (bSSFP) was developed, with progressively increasing flip angles for efficient sampling of the hyperpolarized magnetization. This allowed temporal and volumetric imaging of the [(13)C]urea signal. Regional signal dynamics were quantified for kidneys and liver, and estimates of relative blood flows were derived from the data. Detailed perfusion simulations were performed to validate the methodology. Significant differences were observed in the signal patterns between normal and cancerous murine hepatic tissues. In particular, a 19% reduction in mean blood flow was observed in tumors, with 26% elevation in the tumor rim. The blood flow maps were also compared with metabolic imaging results with hyperpolarized [1-(13)C]pyruvate. Regional assessment of perfusion is possible by imaging of hyperpolarized [(13)C]urea, which is significant for the imaging of cancer.

Establishing a Rodent Stroke Perfusion Computed Tomography Model

Brain computed tomography perfusion imaging in acute stroke may help guide therapy. However, the perfusion thresholds defining potentially salvageable (penumbra) and irreversibly injured (infarct core) tissue require further validation. The aim of this study was to validate infarct core and penumbra perfusion thresholds in a rodent stroke model by developing and optimising perfusion computed tomography imaging, performing serial scanning and correlating scans with final histology. Stroke was induced in male Wistar rats (n=17) using the middle cerebral artery thread-occlusion method. Perfusion computed tomography scans were obtained immediately pre- and postocclusion, and every 30 min for 2.5 h. Histological changes of infarction were assessed after 24 h. High-quality maps of cerebral blood flow and cerebral blood volume were generated at multiple coronal planes after optimisation of contrast injection and scanning parameters. The prestroke absolute cerebral blood flow and cerebral blood volume values (mean ± SD) were 158.2 ± 49.94 ml/min per 100 g and 5.6 ± 1.13 ml per 100 g, respectively. Cerebral blood flow was significantly lower in the infarct region of interest than the contralateral hemisphere region of interest at all time points, except the 0.5 h postocclusion time point. However, cerebral blood volume was only significantly lower in the infarct region of interest than the contralateral hemisphere region of interest at the 1 h and the 1.5 h time points (postocclusion). This study has demonstrated for the first time the feasibility of performing perfusion computed tomography in the most commonly used animal model of stroke. The model will allow definitive studies to determine optimal thresholds and the reliability of perfusion computed tomography measures for infarct core and penumbra.

Contribution of power Doppler blood flow mapping to gray-scale ultrasound for predicting malignancy of adnexal masses in symptomatic and asymptomatic women

Objective To determine the contribution of power Doppler blood flow mapping to gray-scale ultrasound for predicting malignancy of adnexal masses in symptomatic and asymptomatic women. Study design One thousand and ninety-four women with adnexal mass were included. Patients were divided into three groups according to clinical complaints: asymptomatic (group A), patients with symptoms non-suspicious of ovarian cancer (group B) and patients with symptoms suspicious of ovarian cancer (group C). All patients underwent transvaginal power Doppler ultrasound prior to surgery. Any mass in which the echo architecture at B-mode ultrasound was not highly suggestive of benign histology was categorized as questionable. In these cases power Doppler was performed as the second step. Definitive histological diagnosis was used as the standard reference. Sensitivity, specificity, positive likelihood ratio (+LR) and negative likelihood ratio (−LR) were calculated for B-mode diagnosis and B-mode plus Doppler in each group. Results In group A, B-mode was significantly more sensitive (98.1%) than Doppler ultrasound (91.3%) ( p < 0.01). In group B Doppler ultrasound (97.0%) was more specific than B-mode ultrasound (92.2%) ( p < 0.001). In group C Doppler ultrasound (84.0%) was more specific than B-mode ultrasound (68.0%) ( p < 0.001). Positive LR was significantly higher after Doppler evaluation in all groups (30.5 vs 12.8 in group A, 33.2 vs 12.8 in group B and 6.0 vs 3.1 in group C). Conclusions The diagnostic performance of B-mode and power Doppler ultrasound is different depending on patients’ complaints.

Real-time blood flow visualization using the graphics processing unit

Laser speckle imaging (LSI) is a technique in which coherent light incident on a surface produces a reflected speckle pattern that is related to the underlying movement of optical scatterers, such as red blood cells, indicating blood flow. Image-processing algorithms can be applied to produce speckle flow index (SFI) maps of relative blood flow. We present a novel algorithm that employs the NVIDIA Compute Unified Device Architecture (CUDA) platform to perform laser speckle image processing on the graphics processing unit. Software written in C was integrated with CUDA and integrated into a LabVIEW Virtual Instrument (VI) that is interfaced with a monochrome CCD camera able to acquire high-resolution raw speckle images at nearly 10 fps. With the CUDA code integrated into the LabVIEW VI, the processing and display of SFI images were performed also at ∼10 fps. We present three video examples depicting real-time flow imaging during a reactive hyperemia maneuver, with fluid flow through an in vitro phantom, and a demonstration of real-time LSI during laser surgery of a port wine stain birthmark.

Clinical utility of cerebrovascular reactivity mapping in patients with low grade gliomas

To evaluate neurovascular uncoupling (NVU) associated with low grade gliomas (LGG) using blood oxygen level dependent (BOLD) cerebrovascular reactivity mapping. Seven patients with low grade gliomas referred by neurosurgeons for presurgical mapping were included in this pilot study. Cerebrovascular reactivity (CVR) mapping was performed by acquiring BOLD images while patients performed a block-design breath-hold (BH) hypercapnia task. CVR mapping was expressed as BOLD percentage signal change (PSC) from baseline associated with performance of the BH hypercapnia task. Standard T2* Dynamic Susceptibility Contrast perfusion imaging was performed and relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) maps were generated. Structural T1 weighted MR images were also acquired. A correlation analysis between intratumoral normalized (via ratio with contralateral homologous regions) BOLD BH PSC [referred to as (n(CVR))] and intratumoral normalized resting state rCBV (rCBF) values (i.e., n(CBV) and n(CBF), respectively) was performed. No significant correlation was seen between the normalized BOLD BH PSC (i.e., n(CBV)) and n(CBV) or n(CBF). However, the average n(CVR) (median = 0.50, z = -2.28, P = 0.01) was significantly less than 1.0, indicating abnormally reduced vascular responses in the tumor regions relative to normal contralesional homologous regions, whereas the average n(CBV) (median = 0.94, z = -0.92, P = 0.375) and n(CBF) (median = 0.93, z = -1.16, P = 0.25) were not significantly higher or lower than 1.0, indicating iso-perfusion in the tumor regions relative to normal contralesional homologous regions. These findings suggest that in LGG, hyperperfusion that is seen in high grade gliomas is not present, but, nevertheless, abnormally decreased regional CVR is present within and adjacent to LGG. Since the patients all demonstrated at least some residual function attributable to the cortical regions of impaired CVR, but were incapable of producing a BOLD response in these regions regardless of the tasks performed, such regionally decreased CVR is indicative of NVU. The low n(CVR) ratios indicate high prevalence of NVU in this LGG cohort, which is an important consideration in the interpretation of clinical presurgical mapping with functional magnetic resonance (MR) imaging. Our preliminary study shows that BH CVR mapping is clinically feasible and demonstrates an unexpectedly high prevalence of NVU in patients with LGG.

Development of Computer-aided Classification of Alzheimer's Disease Based on Cerebral Blood Flow map by MR imaging

Development of Computer-aided Classification of Alzheimer's Disease Based on Cerebral Blood Flow map by MR imaging

Blood Flow Change Quantification in Cervical Cancer before and during Radiation Therapy Using Perfusion CT

The purpose of this study was to quantify the changes of tumor blood flow (BF) in cervical cancer after radiation therapy by using perfusion computed tomography (CT), and to examine the difference between maximum slope (MS) and single-input one-compartment model (SOCM) methods. Fourteen consecutive patients who received definitive radiation therapy for cervical cancer from October 2009 to February 2010 were enrolled in this study. Blood flow (BF) analyses were performed using both MS and SOCM methods. Quantitative BF maps were created using Body Perfusion (Toshiba Medical Systems, Co. Tokyo, Japan). Perfusion color maps were successfully created by the two analytical methods. BF of the tumors was clearly higher than that of normal cervix, making it possible to distinguish tumor tissue from normal cervical tissue. BF of the tumors after 20 Gy of radiation therapy calculated by the MS method was significantly larger than that before treatment (126.9 vs. 72.2 ml/min/100 ml, median; p < 0.05). Although BF calculated by the MS and SOCM methods showed a positive linear correlation (p < 0.001, r = 0.981), BF calculated by the MS method was lower than that obtained by the SOCM method (103.7 vs. 115.1 ml/min/100 ml, p < 0.01). The change of tumor BF in cervical cancer before and after radiation therapy can be monitored by conducting blood flow analysis using perfusion CT. BF by the MS method was lower than that by the SOCM method, but the two analytical methods correlated well. Perfusion CT may have potential in noninvasive monitoring of vascular and oxygenation status and for guiding adaptive therapy.

Evaluation of angiogenesis of VX2 soft tissue tumor by arterial spin labeling perfusion imaging

Objective To evaluate the relationship between the blood flow values generated from MR arterial spin labeling (ASL) perfusion imaging and pathologic indicators of angiogenesis including microvascular density (MVD) counts and vascular endothelial growth factor (VEGF) expression levels of VX2 carcinoma in rabbit soft tissue. Methods VX2 tumor was inoculated in the muscular tissue of right posterior limbs of 18 healthy New Zealand white rabbits ,on which arterial spin labeling perfusion imaging was performed by using flow sensitive alternating inversion recovery pulse sequence 3 to 4 weeks later. Arterial spin labeling images were transferred to an independent computer for post-processing and blood flow (BF) maps were generated from them. BF values were measured in 2-4 regions of interest (ROIs) for each tumor. The rabbits were sacrificed after MR imaging. The gross specimens of tumors were obtained and tumor tissues were taken from the non-necrotic regions corresponding to ROIs on BF maps. Immunohistochemical staining of the specimens was performed by using CD31 monoclonal antibody to calculate MVD counts, using VEGF antibody to calculate VEGF expression levels. Correlation between BF values and MVD counts as well as between BF values and VEGF expression levels was evaluated using Spearman correlative analysis.Results On BF maps, viable tumor tissues showed high BF values compared with muscle, but there were areas without blood perfusion in some tumors. Under microscope, the microvessels positively stained by CD31 appeared as light brown areas, and the cells positively staied by VEGF showed reddish brown areas within their cytoplasm. Totally 39 pieces of VX2 tumor tissue were analyzeed There was a significant positive correlation between the BF values(M =6. 4 ml · 100 g-1 · min-1 ) and MVD counts(M =6. 8) (r = 0. 906,P ＜ 0. 01 ), and no significant correlation between BF values and VEGF expression levels ( M = 8％ ) ( r =0. 116, P=0.483). Conclusion BF value can be used in evaluating angiogenesis of soft tissue tumor through its reflection of MVD counts, and thus may be helpful in evaluating the prognosis of soft tissue tumor and making plan for their treatment. Key words: Magnetic resonance imaging; Perfusion; Arterial spin labeling; Soft tissue tumor; Angiogenesis

Limitation of pulsed arterial spin labeling technique in the measurement of normal white matter perfusion

Objective To investigate the limitation of quantitative measurement of cerebral blood flow (CBF) of normal white matter by using a single subtraction with thin-slice TI1 periodic saturation (Q2TIPS Ⅱ ) pulsed arterial spin labeling (PASL)technique. Methods Thirty-one patients with brain tumors were examined at 3.0 T MRI system . A second version of quantitative imaging of perfusion using a single subtraction with additional thin-section periodic saturation after inversion and a time delay (Q2TIPS) technique of pulsed arterial spin labeling in the multisection mode and T2* dynamic susceptibility-weighted contrast-enhanced (T2* DSC)MR imaging were both implemented. Cerebral blood flow map obtained from PASL and DSC were reviewed. The regions of interest( ROI )were placed in the region of normal white matter contralateral to the lesion in the proximal and distal slices. In regions of interest, the signal intensity (SI)was measured from the maps of cerebral blood flow map obtained from PASL and DSC. Pair-t test was performed to determine if there were significant signal differences between proximal and distal slices. Pearson linear correlation analysis of signal intensity was performed for values from the same slices of PASL-CBF and DSC-CBF maps. Results In the deep white matter of distal slice, PASL-CBF map showed perfusion deficit while DSC-CBF map showed low CBF in the corresponding brain area. With the increased inversion time,the PASL-CBF map showed obviously improved perfusion signal in deep white matter (but still some perfusion deficit)and slightly decreased perfusion signal in grey matter. The mean signal of normal white matter measured from distal slices of PASL-CBF maps was( -22.1 ±55.5) ml· 100 g-1 · min-1 while it was (89.5 ±45.5) ml. 100 g-1 · min-1 in proximal slices. There was a significant difference of signal intensity from PASL-CBF maps between distal and proximal slices ( t = - 9. 512, P ＜ 0. 01 ＝, while no difference of signal intensity between distal[ (62. 8 ± 29.9) ml · 100 g-1 · min-1] and proximal slices [(57. 1 ±29.6) ml · 100 g-1 · min-1 ]was obtained from DSC-CBF maps(t= -1.607,P＞0.05). There was no significant correlation between PASL-CBF and DSC-CBF in both distal ( r = 0. 093, P ＞ 0. 05 ) and proximal slices ( r = - 0. 234, P ＞ 0. 05). Conclusions PASL has limitation in the accurate quantification of cerebral blood flow of normal white matter. The quantification of CBF was affected by the limitations of the technique itself and the different parameters chosen.. Key words: Brain; Perfusion; Magnetic resonance imaging

Molecular biology: the key to personalised treatment in radiation oncology?

We know considerably more about what makes cells and tissues resistant or sensitive to radiation than we did 20 years ago. Novel techniques in molecular biology have made a major contribution to our understanding at the level of signalling pathways. Before the "New Biology" era, radioresponsiveness was defined in terms of physiological parameters designated as the five Rs. These are: repair, repopulation, reassortment, reoxygenation and radiosensitivity. Of these, only the role of hypoxia proved to be a robust predictive and prognostic marker, but radiotherapy regimens were nonetheless modified in terms of dose per fraction, fraction size and overall time, in ways that persist in clinical practice today. The first molecular techniques were applied to radiobiology about two decades ago and soon revealed the existence of genes/proteins that respond to and influence the cellular outcome of irradiation. The subsequent development of screening techniques using microarray technology has since revealed that a very large number of genes fall into this category. We can now obtain an adequately robust molecular signature, predicting for a radioresponsive phenotype using gene expression and proteomic approaches. In parallel with these developments, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) can now detect specific biological molecules such as haemoglobin and glucose, so revealing a 3D map of tumour blood flow and metabolism. The key to personalised radiotherapy will be to extend this capability to the proteins of the molecular signature that determine radiosensitivity.

Assessment of Acute Antivascular Effects of Vandetanib with High-Resolution Dynamic Contrast-Enhanced Computed Tomographic Imaging in a Human Colon Tumor Xenograft Model in the Nude Rat

Tumor size is not a reliable marker for the assessment of early antivascular effects of antiangiogenics. In the present study, we used 200-µm in-plane high-resolution dynamic contrast-enhanced computed tomography (DCE-CT) to noninvasively assess the immediate antivascular effects of vandetanib in a subcutaneous human colon cancer (LoVo) xenograft model in nude rats and to investigate correlation between changes in CT perfusion parameters and tumor volume or immunohistochemical end points. At 3 to 4 weeks after LoVo cell implantation, the animal was gavaged with either vandetanib (50 mg/kg) or vehicle twice (22 hours apart) and scanned with a preclinical DCE-CT scanner before (0 hour) and after treatment (24 hours). Quantitative maps of blood flow (BF) and volume (BV) of the tumor were calculated from the acquired DCE-CT images. The rats were divided into nonhypovascular, hypovascular, and combined (regardless of vascularity) groups. In the nonhypovascular group, significant decreases in both tumor BF and BV were observed in the vandetanib-treated rats compared with increases in the vehicle-treated rats. A significant decrease in BV was detected in the vandetanib-treated rats in the combined group as well. No differences in tumor growth, vascular endothelial growth factor expression, microvessel density, or apoptosis were observed between vandetanib- and vehicle-treated rats in all three groups. These results demonstrate that BF and BV imaging biomarkers from DCE-CT imaging can be used for rapid monitoring of immediate (24 hours after) antimicrovascular effects of vandetanib on tumors, even in the absence of significant changes of tumor volume or clinically relevant immunohistochemical end points.

Time-resolved three-dimensional magnetic resonance velocity mapping of cardiovascular flow paths in volunteers and patients with Fontan circulation

To apply flow-sensitive magnetic resonance imaging for the evaluation of whole-heart flow characteristics in healthy volunteers and patients with Fontan circulation. Time-resolved three-dimensional magnetic resonance velocity mapping (spatial resolution = 2.5 × 2.8 × 2.8mm(3), temporal resolution = 38.4 ms) was acquired in normal controls and in four Fontan patients with extracardiac total cavopulmonary connection. Data analysis included flow connectivity mapping and flow quantification of arterial and venous blood flow. Haemodynamics in four patients with Fontan circulation were individually evaluated in the aorta, caval veins and left and right pulmonary arteries. In four controls, nine distinct flow features were consistently identified with good feature clarity (median = 2 in 80.6% of readings) and image quality (median = 2 in 75.0% of readings). In patients, a marked variability of flow from the caval veins towards the left and right pulmonary arteries (flow ratio = 1.7 ± 0.6, range 1.2-2.6 vs 1.1 ± 0.1 in controls) was found. Increased offset of the caval venous connection resulted in enhanced pulmonary flow asymmetry. Compared with controls, reduced pulsatility in pulmonary arteries (1.4 ± 0.6 vs 4.1 ± 0.6 in controls) and caval veins (1.2 ± 0.4 vs 2.8 ± 1.1 in controls) were observed. Peak flow was reduced in both superior (22 ± 14 mls(-1) vs 76 ± 7 mls(-1) in controls) and inferior vena cava (61 ± 28 mls(-1) vs 187 ± 42 mls(-1) in controls). This feasibility study demonstrated the potential of whole-heart three-dimensional magnetic resonance velocity mapping to reveal overt haemodynamic differences in surgically palliated congenital heart with similar extracardiac cavopulmonary connection geometry. Future studies are warranted to evaluate its diagnostic impact for improved evaluation of the pre- and postoperative status in the individual patient.

Dynamic CT perfusion imaging of intra-axial brain tumours: differentiation of high-grade gliomas from primary CNS lymphomas

Introduction:Perfusion computed tomography (PCT) allows to quantitatively assess haemodynamic characteristics of brain tissue. We investigated if different brain tumor types can be distinguished from each other using Patlak analysis of PCT data.Methods:PCT data from 43 patients with brain tumours were analysed with a commercial implementation of the Patlak method. Four patients had low-grade glioma (WHO II), 31 patients had glioblastoma (WHO IV) and eight patients had intracerebral lymphoma. Tumour regions of interest (ROIs) were drawn in a morphological image and automatically transferred to maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and permeability (K Trans). Mean values were calculated, group differences were tested using Wilcoxon and Mann Whitney U-tests.Results:In comparison with normal parenchyma, low-grade gliomas showed no significant difference of perfusion parameters (p > 0.05) , whereas high-grade gliomas demonstrated significantly higher values (p < 0.0001 for K Trans, p < 0.0001 for CBV and p = 0.0002 for CBF). Lymphomas displayed significantly increased mean KTrans values compared with unaffected cerebral parenchyma (p = 0.0078) but no elevation of CBV. High-grade gliomas show significant higher CBV values than lymphomas (p = 0.0078).Discussion:PCT allows to reliably classify gliomas and lymphomas based on quantitative measurements of CBV and K Trans.