Extravasation Of Contrast Agent Research Articles

Quantification of experimental venous thrombus resolution by longitudinal nanogold-enhanced micro-computed tomography

IntroductionThe assessment of thrombus size following treatments directed at preventing thrombosis or enhancing its resolution has generally relied on physical or histological methods. This cross-sectional design imposes the need for increased numbers of animals for experiments. Micro-computed tomography (microCT) has been used to detect the presence of venous thrombus in experimental models but has yet to be used in a quantitative manner. In this study, we investigate the use of contrast-enhanced microCT for the longitudinal assessment of experimental venous thrombus resolution. Materials and methodsThrombi induced by stenosis of the inferior vena cava in mice were imaged by contrast-enhanced microCT at 1, 7 and 14days post-induction (n=18). Thrombus volumes were determined longitudinally by segmentation and 3D volume reconstruction of microCT scans and by standard end-point histological analysis at day 14. An additional group of thrombi were analysed solely by histology at 1, 7 and 14days post-induction (n=15). ResultsIVC resident thrombus was readily detectable by contrast-enhanced microCT. MicroCT-derived measurements of thrombus volume correlated well with time-matched histological analyses (ICC=0.75, P<0.01). Thrombus volumes measured by microCT were significantly greater than those derived from histological analysis (P<0.001). Intra- and inter-observer analyses were highly correlated (ICC=0.99 and 0.91 respectively, P<0.0001). Further histological analysis revealed noticeable levels of contrast agent extravasation into the thrombus that was associated with the presence of neovascular channels, macrophages and intracellular iron deposits. ConclusionContrast-enhanced microCT represents a reliable and reproducible method for the longitudinal assessment of venous thrombus resolution providing powerful paired data.

On the Use of DSC-MRI for Measuring Vascular Permeability.

Contrast agent extravasation has been shown to confound brain tumor perfusion measurements with DSC-MR imaging, necessitating the use of correction techniques (eg, Weisskoff, Bjornerud). Leakage parameters (K2 and K(a)) postulated to reflect vessel permeability can be extracted from these correction methods; however, the biophysical interpretation of these parameters and their relationship to commonly used MR imaging measures of vascular permeability (eg, contrast agent volume transfer constant, [K(trans)]) remain unclear. Given that vascular density, as assessed by blood volume, and vascular permeability, as reflected by K(trans) (and potentially K2 or K(a)), report on unique and clinically informative vascular characteristics, there is a compelling interest to simultaneously assess these features. We acquired multiecho DSC-MR imaging data, allowing the simultaneous computation and voxelwise comparison of single- and dual-echo derived measures of K2, K(a) and K(trans) in patients with glioma. This acquisition enabled the investigation of competing T1 and T2* leakage effects and TE dependency on these parameters. K2 and K(a) displayed nonsignificant (P = .150 and P = .060, respectively) voxelwise linear correlations with K(trans), while a significant (P < .001) inverse relationship was observed between K2 and Ka (coefficient of determination [r(2)] = 0.466-0.984). Significantly different (P < .005) mean estimates were found between voxels exhibiting predominately T1 and T2* effects for K2 and K(a). K(trans), however, was observed to be similar between these voxels (0.109 versus 0.092 minutes(-1)). Significant differences (P < .001) in extracellular-extravascular volume fraction (v(e)) (0.285 versus 0.167) were also observed between cohorts. Additionally, K2 and K(a) were found to have a significant quadratic relationship (P = .031 and P = .005, respectively) with v(e). Estimates of vascular permeability in brain tumors may be simultaneously acquired from multiple-echo DSC-MR imaging via K(trans); however, caution should be used in assuming a similar relationship for K2 and K(a).

Investigation of medical intervention with fatal outcome: the impact of post-mortem CT and CT angiography.

Post-mortem computed tomography (PMCT) has been proven for its appropriateness to become an integral part of routine pre-autoptic forensic investigations either in the field of forensic investigation of fatal medical error or in hospital quality management. The autoptic investigation of unexpected and peri-interventional deaths can be usefully guided by post-mortem imaging which offers significant added value in the documentation of misplacement of medical devices before dissection with the risk of artificial relocation and the detection of iatrogenic air embolism. Post-mortem CT angiography (PMCTA) augments PMCT in the search for sources of hemorrhages and for the documentation of vascular patency and unimpaired perfusion after general and cardiovascular surgery or transvascular catheter-assisted interventions. Limitations of PMCT and PMCTA in medical error cases are method-related or time-dependent including artifacts by early post-mortem tissue change. Thromboembolic complications including pulmonary embolism, the differentiation of ante- and post-mortem coagulation and the detection of myocardial infarction remain areas with compromised diagnostic efficiency as compared to autopsy. Furthermore, extended survival periods after a complication in question impedes visualization of contrast agent extravasation at vascular leakage sites. PMCT and PMCTA contribute substantially for proving a correct interventional approach and guide forensic or clinical autopsy in the reconstruction of adverse medical events with fatal outcome. Post-mortem imaging could also assume a new role as an alternative in a clinicopathological setting if autopsy is not achievable when the probability in the individual case is acceptable to answer specific questions.

Interventional MRI-guided local delivery of agents into swine bile duct walls using MR-compatible needle-integrated balloon catheter system.

The purpose of this study was to investigate the feasibility of interventional MRI-guided local agent delivery into pig common bile duct (CBD) walls using a newly designed MR-compatible, needle-integrated balloon catheter system. We first designed a needle-integrated balloon catheter system that comprised of a 22 G MR-compatible Chiba biopsy needle and a conventional 12 mm × 2 cm balloon catheter. Under fluoroscopy guidance, a custom needle-balloon system was positioned in the target CBD via a transcholecystic access. T1-weighted MRI was used to localize and reposition the needle-balloon system in the target. A 0.5 mL mixture of motexafin gadolinium (MGd) and trypan blue dye as well as 5-fluorouracil was delivered into the CBD wall through the needle-balloon system. Post-infusion T1-weighted MRI was obtained and contrast-to-noise ratios (CNRs) of CBD walls of pre- and post-MGd-blue infusions were compared by a paired t-test. In addition, post-infusion x-ray cholangiography was achieved to evaluate the potential injuries of CBDs by the needle-balloon system. Subsequent histologic analysis was performed to correlate and confirm the imaging findings. A post-infusion cholangiogram did not show any extravasation of contrast agent, indicating no procedure-related damage to the CBDs. MRI demonstrated clear enhancement of the target bile duct walls infused with MGd-trypan blue dye with average penetration depth of 4.7 ± 1.2 mm and an average MGd perfusion length of 21 ± 1.5 mm in the bile ducts and their surrounding tissues. The average CNR of the post-infusion bile ducts was significant higher than that of the pre-infusion bile ducts (110.6 ± 22 versus 5.7 ± 2.8, p < 0.0001). Histology depicted the blue dye staining and red fluorescence of MGd through the target CBD walls, which was well correlated with the imaging findings. It is feasible to use the new MR-compatible, needle-integrated balloon catheter system for intrabiliary local agent delivery into CBD walls under MRI guidance, which may open new avenues for efficient management of pancreatobiliary malignancies using MR-guided interventional oncology.

Imaging of thoracic aortic injury

Isthmic aortic rupture or disruption should be systematically sought when there is high kinetic energy trauma to the thorax. This condition is extremely serious and life threatening. It needs to be diagnosed rapidly but diagnostic pitfalls must be avoided. CT angiography is the standard examination. The main CT signs of rupture or disruption of the thoracic aorta are periaortic hematoma, intimal flap, pseudo-aneurysm and contrast agent extravasation. There are three types of lesion: intimal, subadventitial or pseudo-aneurysmal, and complete rupture with lesion of the three tunicae, and it is important to grade them for better therapeutic management. The main diagnostic pitfalls of the CT scan are the presence of a ductus diverticulum and post-isthmic fusiform dilatation. Associated lesions must not be overlooked. The most common are ruptures of the aortic root and the thoracic aorta in the diaphragmatic hiatus.

Perivascular microglia promote blood vessel disintegration in the ischemic penumbra.

The contribution of microglia to ischemic cortical stroke is of particular therapeutic interest because of the impact on the survival of brain tissue in the ischemic penumbra, a region that is potentially salvable upon a brain infarct. Whether or not tissue in the penumbra survives critically depends on blood flow and vessel perfusion. To study the role of microglia in cortical stroke and blood vessel stability, CX3CR1(+/GFP) mice were subjected to transient middle cerebral artery occlusion and then microglia were investigated using time-lapse two-photon microscopy in vivo. Soon after reperfusion, microglia became activated in the stroke penumbra and started to expand cellular protrusions towards adjacent blood vessels. All microglia in the penumbra were found associated with blood vessels within 24 h post reperfusion and partially fully engulfed them. In the same time frame blood vessels became permissive for blood serum components. Migration assays in vitro showed that blood serum proteins leaking into the tissue provided molecular cues leading to the recruitment of microglia to blood vessels and to their activation. Subsequently, these perivascular microglia started to eat up endothelial cells by phagocytosis, which caused an activation of the local endothelium and contributed to the disintegration of blood vessels with an eventual break down of the blood brain barrier. Loss-of-microglia-function studies using CX3CR1(GFP/GFP) mice displayed a decrease in stroke size and a reduction in the extravasation of contrast agent into the brain penumbra as measured by MRI. Potentially, medication directed at inhibiting microglia activation within the first day after stroke could stabilize blood vessels in the penumbra, increase blood flow, and serve as a valuable treatment for patients suffering from ischemic stroke.

64排螺旋CT增强扫描中碘对比剂外渗的护理干预及应对措施

Objective: To investigate 64 row spiral CT enhanced scan iodine contrast agent extravasation of emergency nursing intervention and countermeasures, to reduce the adverse reactions caused by contrast medium extravasation and tissue necrosis. Methods : Collected in February 2011 to January 2013, the hospital CT room 32 cases of adverse reactions, 5 cases occurred immediately after extravasation of contrast using discount comfeel plus transparent dressing stick, using its promoting inflammatory cells absorption and metabolism, reduce pain; Use its dissolving fibrin, prevent the iodine contrast agent to stimulate vein caused by continuous high pressure; Use water of colloid autolyzed debridement, absorb excess wound exudate. Results : 5 patients with iodine contrast agent extravasation, apply immediately after extravasation of contrast with comfeel plus transparent dressing stick, swelling was controlled in time, no longer continue to increase, 2-3 days to heal. Conclusion : Extravasation of comfeel plus transparent dressing stick for iodine contrast curative effect is distinct, the operation method is simple and practical, safe and reliable, which saves the nursing time, reduces the patient's pain.

Postinterventional subarachnoid haemorrhage after endovascular stroke treatment with stent retrievers.

The purpose of this paper is to investigate the clinical significance of postinterventional subarachnoid hyperdensities (PSH) after endovascular mechanical thrombectomy in acute ischemic stroke. We analysed clinical and radiological data of 113 consecutive patients who received postinterventional CT scans within 4.5 h after mechanical thrombectomy. PSH was present in 27 of 113 patients (24%). Extravasation of contrast agent was observed during intervention in only 6 of 27 cases (22%). There was consecutive haemorrhagic transformation in four patients with PSH (p = 0.209, Fisher's exact test). Preinterventional predictors for the occurrence of PSH in our series were a long interval between clinical onset and recanalization (p = 0.028), a long procedure time (p = 0.010), and a high number of recanalization attempts (p = 0.001). PSH had no significant impact on clinical outcome (modified Rankin Scale) at discharge (p = 0.419) or at 3 months (p = 0.396). There were no significant correlations between PSH and thrombectomy devices (Solitaire: p = 0.433, Trevo Pro: p = 0.124). PSH after endovascular mechanical thrombectomy in acute ischemic stroke are likely to occur in complicated cases in which more than one revascularisation attempt is performed. PSH per se do not appear to be associated with an impaired clinical outcome or an elevated risk for consecutive haemorrhage.

Intratumor mapping of intracellular water lifetime: metabolic images of breast cancer?

Shutter-speed pharmacokinetic analysis of dynamic-contrast-enhanced (DCE)-MRI data allows evaluation of equilibrium inter-compartmental water interchange kinetics. The process measured here – transcytolemmal water exchange – is characterized by the mean intracellular water molecule lifetime (τi). The τi biomarker is a true intensive property not accessible by any formulation of the tracer pharmacokinetic paradigm, which inherently assumes it is effectively zero when applied to DCE-MRI. We present population-averaged in vivo human breast whole tumor τi changes induced by therapy, along with those of other pharmacokinetic parameters. In responding patients, the DCE parameters change significantly after only one neoadjuvant chemotherapy cycle: while Ktrans (measuring mostly contrast agent (CA) extravasation) and kep (CA intravasation rate constant) decrease, τi increases. However, high-resolution, (1 mm)2, parametric maps exhibit significant intratumor heterogeneity, which is lost by averaging. A typical 400 ms τi value means a trans-membrane water cycling flux of 1013 H2O molecules s−1/cell for a 12 µm diameter cell. Analyses of intratumor variations (and therapy-induced changes) of τi in combination with concomitant changes of ve (extracellular volume fraction) indicate that the former are dominated by alterations of the equilibrium cell membrane water permeability coefficient, PW, not of cell size. These can be interpreted in light of literature results showing that τi changes are dominated by a PW(active) component that reciprocally reflects the membrane driving P-type ATPase ion pump turnover. For mammalian cells, this is the Na+,K+-ATPase pump. These results promise the potential to discriminate metabolic and microenvironmental states of regions within tumors in vivo, and their changes with therapy.

Rapid-Steady-State-T1 signal modeling during contrast agent extravasation: toward tumor blood volume quantification without requiring the arterial input function.

This study demonstrates how to quantify the tumor blood volume fraction (BVf) using the dynamic Rapid-Steady-State-T1 (RSST1 )-MRI method despite contrast agent (CA) leakage and without arterial input function (AIF) determination. For vasculature impermeable to CAs, the BVf is directly quantified from the RSST1 signal amplitude. In case of CA extravasation, we propose a two-compartment model to describe the dynamic RSST1 signal increase. We applied the mathematical model in a pilot-study on a RG2-glioma model to compare extravasation of two Gd-based CAs. The BVf quantification using the mathematical model in a C6-glioma model (n = 8) with the clinical CA Gd-DOTA was validated using a ΔR2 *-steady-state MRI method with an USPIO and by immunohistochemical staining of perfused vessels labeled with Hoechst-33342 dye in the same rats. BVf in tumor and in healthy brain tissues (0.034 ± 0.005 and 0.026 ± 0.004, respectively) derived from the dynamic RSST1 signal were confirmed by ΔR2 *-steady-state MRI (0.036 ± 0.003 and 0.027 ± 0.002, respectively, correlation coefficient rS = 0.74) and by histology (0.036 ± 0.003 and 0.025 ± 0.004 respectively, rS = 0.87). Straightforward tumor BVf quantification without AIF determination is demonstrated in presence of CA leakage. The method will facilitate angiogenesis assessment in longitudinal neuro-oncologic studies in particular when monitoring the response to antiangiogenic therapies.

EComment. Initial workup and decision-making regarding coexistence of massive haemothorax and haemopericardium

We read with great interest the article 'Right massive haemothorax as the presentation of blunt cardiac rupture: the pitfall of coexisting pericardial laceration' by Chen et al. [1]. This well-presented case highlights a dual emergency and its successful approach. The discussion section, however, includes a number of possible causes that may be responsible for blunt traumatic haemothorax, without mentioning injury of the diaphragm. Traumatic diaphragm injury accounts for almost 3.3% of blunt trauma cases [2]. Three years ago, we faced and reported a rare case of haemothorax due to blunt injury in a patient with hereditary rib exostosis that caused diaphragm penetration [3]. Several other case reports consider not only traumatic diaphragm rupture, but also vascular damage by pressure trauma as an aetiological factor for haemothorax. In addition, there are cases where the disrupted spleen is herniated through the diaphragm in the thorax, causing a haemothorax. Therefore, massive haemothorax should not always focus attention to the chest and intrathoracic causes of haemodynamic instability. If such injuries are not recognized and approached properly, potential for survival is limited. According to the latest guidelines, ultrasound can reliably be used to identify and measure pleural or pericardial effusion, while computed tomography (CT) of the chest is indicated in patients with persistent opacity on chest radiograph after tube thoracostomy [4]. In our case there was no massive bleeding, and our initial imaging workup consisted of a chest X-ray and an ultrasound scan. Decisive diagnosis, however, was obtained after a chest CT scan, which indicated surgical treatment via an anterolateral mini-thoracotomy. Since patients with traumatic lesions and haemorrhagic pleural effusion usually have multiple bleeding sources, contrast-enhanced CT is generally considered necessary to identify the bleeding points, document their anatomic relationships, detect extravasation of contrast agent, and reveal any additional organ injury. Current studies on massive haemothorax, however, suggest that patient's physiology should be the primary indication for surgical intervention, and advocate thoracotomy, regardless of the mechanism of injury [4]. On the other hand, in case of haemopericardium, most reports are in favour of sternotomy [5]. This article presents a rare coexistence of massive haemothorax and haemopericardium. Is it correct to proceed with a thoracotomy based on clinical evidence and patient's physiology without a CT scan? Is median sternotomy a better operative option regarding this dual entity? According to the Authors, the subxiphoid approach shifted to median sternotomy immediately because of catastrophic haemorrhage from pericardial window. Should they have avoided the subxiphoid window and performed a posterolateral thoracotomy right after focus assessment sonography? In order to answer these questions, an algorithm of initial imaging and interventional workup must be established. We look forward to reading further analyses on the subject.

Extravasation into brain and subsequent spread beyond the ischemic core of a magnetic resonance contrast agent following a step-down infusion protocol in acute cerebral ischemia.

BackgroundLimiting expansion of the ischemic core lesion by reinstating blood flow and protecting the penumbral cells is a priority in acute stroke treatment. However, at present, methods are not available for effective drug delivery to the ischemic penumbra. To address these issues this study compared the extravasation and subsequent interstitial spread of a magnetic resonance contrast agent (MRCA) beyond the ischemic core into the surrounding brain in a rat model of ischemia-reperfusion for bolus injection and step-down infusion (SDI) protocols.MethodsMale Wistar rats underwent middle cerebral artery (MCA) occlusion for 3 h followed by reperfusion. Perfusion-diffusion mismatched regions indicating the extent of spread were identified by measuring cerebral blood flow (CBF) deficits by arterial spin-labeled magnetic resonance imaging and the extent of the ischemic core by mapping the apparent diffusion coefficient (ADC) of water with diffusion-weighted imaging. Vascular injury was assessed via MRCA, gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) penetration, by Look-Locker T1-weighted MR imaging after either a bolus injection (n = 8) or SDI (n = 6). Spatial and temporal expansion of the MRCA front during a 25 min imaging period was measured from images obtained at 2.5 min intervals.ResultsThe mean ADC lesion was 20 ± 7% of the hemispheric area whereas the CBF deficit area was 60 ± 16%, with the difference between the areas suggesting the possible presence of a penumbra. The bolus injection led to MRCA enhancement with an area that initially spread into the ischemic core and then diminished over time. The SDI produced a gradual increase in the area of MRCA enhancement that slowly enlarged to occupy the core, eventually expanded beyond it into the surrounding tissue and then plateaued. The integrated area from SDI extravasation was significantly larger than that for the bolus (p = 0.03). The total number of pixels covered by the SDI at its maximum was significantly larger than the pixels covered by bolus maximum (p = 0.05).ConclusionsThese results demonstrate that the SDI protocol resulted in a spread of the MRCA beyond the ischemic core. Whether plasma-borne acute stroke therapeutics can be delivered to the ischemic penumbra in a similar way needs to be investigated.

Acceleration of conventional data acquisition in dynamic contrast enhancement: comparing keyhole approaches with compressive sensing.

Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) has become a valuable clinical tool for cancer diagnosis and prognosis. DCE MRI provides pharmacokinetic parameters dependent on the extravasation of small molecular contrast agents, and thus high temporal resolution and/or spatial resolution is required for accurate estimation of parameters. In this article we investigate the efficacy of 2 undersampling approaches to speed up DCE MRI: a conventional keyhole approach and compressed sensing-based imaging. Data reconstructed from variants of these methods has been compared with the full k-space reconstruction with respect to data quality and pharmacokinetic parameters Ktrans and ve. Overall, compressive sensing provides better data quality and reproducible parametric maps than key-hole methods with higher acceleration factors. In particular, an undersampling mask based on a priori precontrast data showed high fidelity of reconstructed data and parametric maps up to 5× acceleration.

A Case of Gastric Ulcer Bleeding by Direct Connection to the Splenic Artery

Gastric ulcer bleeding is commonly encountered in emergency situations for gastroenterologist. Usually depth of gastric ulcer does not exceed the muscle layer. We report a case of a 67-year-old male with massive gastric ulcer bleeding caused by direct connection to the splenic artery. Bleeding control was not effectively performed by endoscopy due to massive bleeding with unstable vital sign. Angiography for embolization was performed. Active extravasation of contrast agents at the splenic artery stenosis was noted on splenic arteriogram. Bleeding stopped after embolization with histoacryl and lipiodol was successfully performed. After 1 month, complete ulcer healing was confirmed by follow up endoscopy. There was no evidence of invasive disease on biopsy. (Korean J Helicobacter Up Gastrointest Res 2014;14:211-214)

Muscle-based pharmacokinetic modeling of marrow perfusion for osteoporotic bone in females.

The pharmacokinetic model has been widely used in tissue perfusion analysis, such as bone marrow perfusion. In the modeling process, the arterial input function is important to guarantee the reliability of the fitting result. However, the arterial input function is variable and hard to control, which makes it difficult to compare results across different studies. The purpose of this study was to establish a muscle-based pharmacokinetic model for bone marrow perfusion without using arterial input function. Erector spinae muscle around the vertebral body was selected as the reference region. The study was carried out in elderly females with different bone mineral densities (normal, osteopenia, and osteoporosis). Quantitative parameters were extracted from the pharmacokinetic model. Parameter K trans,BM (contrast agent extravasation rate constants for blood perfusion of the bone marrow) showed a significant reduction in subjects with lower bone mineral density, which is consistent with previous studies. However, muscle perfusion parameters remained unchanged among different groups. The results indicated that the muscle-based model was stable for bone marrow perfusion modeling. Additionally, nonsignificant change in muscle parameters indicated that the diminished perfusion is only a local rather than a systematic change in the bone marrow for osteoporosis.

Improved outcomes with direct percutaneous CT guided lumbar synovial cyst treatment: advanced approaches and techniques

PurposeTo determine if lumbar synovial cyst rupture in symptomatic patients results in improved clinical outcome when using direct tandem and/or coaxial percutaneous CT guided techniques.Materials and methods20 patients with unilateral...

Multimodal imaging enables early detection and characterization of changes in tumor permeability of brain metastases

Our goal was to develop strategies to quantify the accumulation of model therapeutics in small brain metastases using multimodal imaging, in order to enhance the potential for successful treatment. Human melanoma cells were injected into the left cardiac ventricle of immunodeficient mice. Bioluminescent, MR and PET imaging were applied to evaluate the limits of detection and potential for contrast agent extravasation in small brain metastases. A pharmacokinetic model was applied to estimate vascular permeability. Bioluminescent imaging after injecting d-luciferin (molecular weight (MW) 320D) suggested that tumor cell extravasation had already occurred at week 1, which was confirmed by histology. 7T T1w MRI at week 4 was able to detect non-leaky 100μm sized lesions and leaky tumors with diameters down to 200μm after contrast injection at week 5. PET imaging showed that 18F-FLT (MW 244Da) accumulated in the brain at week 4. Gadolinium-based MRI tracers (MW 559Da and 2.066kDa) extravasated after 5weeks (tumor diameter 600μm), and the lower MW agent cleared more rapidly from the tumor (mean apparent permeabilities 2.27×10−5cm/s versus 1.12×10−5cm/s). PET imaging further demonstrated tumor permeability to 64Cu-BSA (MW 65.55kDa) at week 6 (tumor diameter 700μm). In conclusion, high field T1w MRI without contrast may improve the detection limit of small brain metastases, allowing for earlier diagnosis of patients, although the smallest lesions detected with T1w MRI were permeable only to d-luciferin and the amphipathic small molecule 18F-FLT. Different-sized MR and PET contrast agents demonstrated the gradual increase in leakiness of the blood tumor barrier during metastatic progression, which could guide clinicians in choosing tailored treatment strategies.

Parietal pleural hematoma: plausible aortic dissection in an octogenarian on multiple antiplatelets, coumadin and oral steroids

An 84-year-old male on oral steroids, coumadin and multiple antiplatelets for stented superficial femoral artery presented to our hospital with chest oppression. His CT scan showed cardiac tamponade with periaortic hematoma. At first, sealed rupture of aortic dissection with thrombosed false lumen was suspected. However, delayed enhancement view revealed extravasation of contrast agent, which appeared to drain into the pericardium or pericardial space. Emergency thoracotomy revealed normal aorta with several small spurting vessels of pulmonary side of the pericardium. To the best of our knowledge, this is the first reported case in the literature of a parietal pleural hematoma without known cause such as malignancy or hematologic disorders.

Abstract 1559: Evaluation of MR imaging biomarkers of the vascular and infiltrative phenotype in intracranial MDA-MB-231 tumors.

Abstract Tumors growing in the brain often invade into the parenchyma and co-opt the existing vasculature leaving the blood brain barrier (BBB) intact; extravasation of the Gd-DTPA contrast agent used in MRI is therefore precluded. Anti-angiogenic agents can restore the compromised BBB of neovascular regions resulting in ‘pseudoresponse’ in human glioblastoma (GBM), and preclinical brain metastasis models. Non-invasive imaging strategies are required to accurately interrogate brain specific growth patterns. Preclinical models that faithfully emulate infiltrative gliomas are limited. Intracranial implantation of MDA-MB-231 breast cancer cells results in tumors exhibiting substantial local invasion, principally occurring along existing blood vessels. Multiparametric MRI was used to identifying sensitive biomarkers of infiltrative tumor growth in this model. Alteration in the vascular phenotype was assessed in response to pan-VEGFR inhibitor cediranib or cross reactive human/mouse anti-VEGF-A antibody B20-4.1.1. Intracranial MDA-MB-231 tumors were heterogeneous; areas of high apparent diffusion coefficient (ADC, mm2s−1), a biomarker of cellularity, correlated with the most hyperintense regions on T2-weighted images and areas of histologically confirmed edema. Regions of high Gd-DTPA extravasation were distinct from the areas of high ADC, but correlated with regions of high fractional blood volume (fBV) detected using intravascular USPIO particles. Infiltrative regions identified on H&amp;E images corresponded to areas of limited Gd-DTPA leakage and low fBV. Cediranib (3 x 6mg/kg) caused significant tumor growth delay after 48h compared to controls (cediranib 160 ± 9% pre-treatment volume, vehicle 210 ± 14%, p&amp;lt;0.05, unpaired t-test). A 50% reduction in Ktrans (min−1), a compound biomarker of permeability/perfusion, was observed following cediranib treatment (p&amp;lt;0.05, paired t-test). Perfused tumor area, assessed using Hoechst 33342, was lower in treated tumors (cediranib 5.4 ± 0.6%, vehicle 9.1 ± 1.5%, p&amp;lt;0.05), confirming reduced vascular function. Cediranib also led to a 9% reduction in tumor ADC (p&amp;lt;0.05), possibly due to resolution of edema, as observed in GBM patients. A single 10mg/kg dose of B20-4.1.1 resulted in significant tumor growth delay over 48h (B20-4.1.1 120 ± 18%, control antibody 230 ± 8%) and a 58% reduction in Ktrans (p&amp;lt;0.05), but no change in ADC was observed. BBB integrity following treatment is being evaluated to inform on the contributions of its restoration, and altered vascular function, to the observed changes in vascular imaging biomarkers. Intracranial MDA-MB-231 tumors provide a useful model for the development of imaging biomarkers of the infiltrative and vascular phenotype of tumors in the brain, which are essential for the assessment of the novel invasive orthotopic glioma models currently being developed, and their response to therapeutics. Citation Format: Jessica KR Boult, Alexa Jury, Sergey Popov, Lara Perryman, Gary Box, Chris Jones, Suzanne A. Eccles, Simon P. Robinson. Evaluation of MR imaging biomarkers of the vascular and infiltrative phenotype in intracranial MDA-MB-231 tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1559. doi:10.1158/1538-7445.AM2013-1559

Simultaneous Perfusion and Permeability Measurements Using Combined Spin- and Gradient-Echo MRI

The purpose of this study was to estimate magnetic resonance imaging-based brain perfusion parameters from combined multiecho spin-echo and gradient-echo acquisitions, to correct them for T₁₋, T₂₋, and T₂₋*-related contrast agent (CA) extravasation effects, and to simultaneously determine vascular permeability. Perfusion data were acquired using a combined multiecho spin- and gradient-echo (SAGE) echo-planar imaging sequence, which was corrected for CA extravasation effects using pharmacokinetic modeling. The presented method was validated in simulations and brain tumor patients, and compared with uncorrected single-echo and multiecho data. In the presence of CA extravasation, uncorrected single-echo data resulted in underestimated CA concentrations, leading to underestimated single-echo cerebral blood volume (CBV) and mean transit time (MTT). In contrast, uncorrected multiecho data resulted in overestimations of CA concentrations, CBV, and MTT. The correction of CA extravasation effects resulted in CBV and MTT estimates that were more consistent with the underlying tissue characteristics. Spin-echo perfusion data showed reduced large-vessel blooming effects, facilitating better distinction between increased CBV due to active tumor progression and elevated CBV due to the presence of cortical vessels in tumor proximity. Furthermore, extracted permeability parameters were in good agreement with elevated T1-weighted postcontrast signal values.