Significant Changes In Perfusion Research Articles

Lactate and base excess (BE) as markers of hypoperfusion and mortality in traumatic hemorrhagic shock in patients undergoing Damage Control: a historical cohort.

hemorrhagic shock is a significant cause of trauma-related deaths in Brazil and worldwide. This study aims to compare BE and lactate values at ICU admission and twenty-four hours after in identifying tissue hypoperfusion and mortality. examines a historical cohort of trauma patients over eitheen years old submittet to damage control resuscitation approch upon hospital admission and were then admitted to the ICU. We collected and analyzed ISS, mechanism and type of trauma, need for renal replacement therapy, massive transfusion. BE, lactate, pH, bicarbonate at ICU admission and twenty-four hours later, and mortality data. The patients were grouped based on their BE values (≥-6 and <-6mmol/L), which were previously identified in the literature as predictors of severity. They were subsequently redivided using the most accurate values found in this sample. In addition to performing multivariate binary logistic regression. The data were compared using several statistical tests due to diversity and according to the indication for each variable. there were significant changes in perfusion upon admission to the Intensive Care Unit. BE is a statistically significant value for predicting mortality, as determined by using values from previous literature and from this study. the results demonstrate the importance of monitoring BE levels in the prediction of ICU mortality. BE proves to be a valuable bedside marker with quick results and wide availability.

Cerebral perfusion changes in acute subdural hematoma

IntroductionAcute subdural hematoma (aSDH) is one of the main causes of high mortality and morbidity in traumatic brain injury. Prognosis is poor due to the rapid volume shift and mass effect. Cerebral perfusion is likely affected in this condition. This study quantifies perfusion changes in aSDH using early ER polytrauma CT with perfusion imaging (CTP).MethodsData of 54 patients with traumatic aSDH were retrospectively collected. Glasgow Coma scale (GCS), perfusion parameters, therapeutic decisions and imaging data including hematoma thickness, midline shift, and hematoma localization were analyzed. The cortical perfusion parameters of each hemisphere, the area anterior to the hematoma (AAH), area below the hematoma (ABH), area posterior to the hematoma (PAH), and corresponding mirrored contralateral regions were determined.ResultsWe found a significant difference in Tmax in affected and unaffected whole-hemisphere data (mean 4.0 s vs. 3.3 s, p < 0.05) and a significantly different mean for Tmax in ABH and for the corresponding mirrored area (mABH) (mean 3.8 s vs. 3.1 s, p < 0.05). No significant perfusion changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were found.ConclusionThere was a significant elevation of time to maximum (Tmax) values in the underlying cortical area of aSDH. Possible pathophysiological explanations, the influence on immediate surgical decision-making and further therapeutic consequences have to be evaluated.

MR-based follow-up after brachytherapy and proton beam therapy in uveal melanoma

PurposeMRI is increasingly used in the diagnosis and therapy planning of uveal melanoma (UM). In this prospective cohort study, we assessed the radiological characteristics, in terms of anatomical and functional imaging, of UM after ruthenium-106 plaque brachytherapy or proton beam therapy (PBT) and compared them to conventional ultrasound.MethodsTwenty-six UM patients were evaluated before and 3, 6 and 12 months after brachytherapy (n = 13) or PBT (n = 13). Tumour prominences were compared between ultrasound and MRI. On diffusion-weighted imaging, the apparent diffusion value (ADC), and on perfusion-weighted imaging (PWI), the time-intensity curves (TIC), relative peak intensity and outflow percentages were determined. Values were compared between treatments and with baseline.ResultsPre-treatment prominences were comparable between MRI and ultrasound (mean absolute difference 0.51 mm, p = 0.46), but larger differences were observed post-treatment (e.g. 3 months: 0.9 mm (p = 0.02)). Pre-treatment PWI metrics were comparable between treatment groups. After treatment, brachytherapy patients showed favourable changes on PWI (e.g. 67% outflow reduction at 3 months, p < 0.01). After PBT, significant perfusion changes were observed at a later timepoint (e.g. 38% outflow reduction at 6 months, p = 0.01). No consistent ADC changes were observed after either treatment, e.g. a 0.11 × 10−3mm2/s increase 12 months after treatment (p = 0.15).ConclusionMR-based follow-up is valuable for PBT-treated patients as favourable perfusion changes, including a reduction in outflow, can be detected before a reduction in size is apparent on ultrasound. For brachytherapy, a follow-up MRI is of less value as already 3 months post-treatment a significant size reduction can be measured on ultrasound.

Short duration – low intensity isometric plantar flexion increases distal perfusion: observations from a healthy cohort

Controlled physical activity might help as a preventive and therapeutic tool in vascular pathology. In this study we aimed to understand how lower limb exercise impacts perfusion in a healthy cohort. The study involved a convenience sample of eighteen previously selected healthy individuals of both sexes (n=9 each), mean age 32.8 ± 12.7 years. Procedures respected all principles of good clinical practice. Blood perfusion changes were simultaneously assessed in the dorsal region of both feet by laser Doppler flowmetry (LDF) and polarised spectroscopy (PSp). Measurements were taken at baseline, after stabilization (phase I), following 1 minute of bipedal isometric plantar flexion (phase II), and during recovery (phase III). Descriptive and comparative statistics were performed. Plantar flexion evoked significant perfusion changes in both feet, but in opposite directions – increasing with LDF and decreasing with PSp. These changes indicate that this approach promotes an adaptive mobilisation of blood from superficial to the deeper plexus. No significant changes in arterial blood pressure or cardiac frequency were detected. This manoeuvre, needing no specialised supervision, is capable of promoting significant perfusion changes in the lower limb, showing potential to be further explored in future studies with a prospective design in a preventive/recovery context. Keywords: plantar flexion; foot perfusion; laser Doppler flowmetry; polarised spectroscopy; PAHR - prompt adaptive hemodynamical response; physical activity; home-health

SPECT activation patterns in psychogenic non-epileptic seizures in temporal lobe epilepsy patients

IntroductionThe diagnosis of psychogenic non-epileptic seizures (PNES) can often be challenging. When video-electroencephalography (EEG) is not conclusive, single-photon emission computed tomography (SPECT) can be useful by quantifying changes in regional cerebral blood flow (rCBF). MethodsWe conducted a retrospective case-control study in adult patients with pharmacoresistant temporal lobe epilepsy (TLE). Those patients with an ictal SPECT obtained during an event finally diagnosed as PNES were included as cases (PNES+). The control group consisted of patients with TLE without PNES (PNES-). Clinical episodes were analysed and classified according to PNES subtypes. Subtraction ictal SPECT coregistered to MRI (SISCOM) analysis was performed for the detection of areas with significant changes in perfusion compared to individual interictal studies. Group comparisons in SPM12 included paired t-tests of ictal vs. interictal studies in each group of temporal lobe seizures and PNES events. ResultsTen patients with TLE and PNES were included. We found no patterns of regional hyperperfusion typical of TLE seizures during the PNES events. In two of these cases, an ictal SPECT during a confirmed epileptic seizure was also obtained, showing antero-mesial temporal lobe hyperperfusion. Group comparisons between ictal and interictal SPECTs showed increased rCBF in the temporal lobe with reduced perfusion in the default mode network areas and cerebellum during temporal lobe seizures in PNES- patients and decreased perfusion restricted to the posterior parietal cortex without significant rCBF increases in PNES events. ConclusionsIctal SPECT can be a helpful tool to characterize rCBF changes in PNES and for differential diagnosis with seizures in TLE patients.

Sex-related differences in arterial spin-labelled perfusion of metabolically active brain structures in neonatal hypoxic–ischaemic encephalopathy

To investigate the sex-related differences in arterial spin-labelled (ASL) perfusion of metabolically active brain structures in neonatal hypoxic-ischaemic encephalopathy (HIE). Seventy-three term neonates were identified for a retrospective case-control study following an institutional review board (IRB) approved protocol. The cerebral pulsed arterial spin labelling values were compared by permutation test to identify metabolically active brain structures with significant perfusion changes between 10 male controls and eight female controls, and between 31 HIE males and 24 HIE females. In the perfusion comparison between HIE male and female neonates, significantly lower perfusion was found in the thalamus in males (p=0.02). The other brain clusters, including basal ganglia, hippocampus cluster, cingulate gyrus cluster, brainstem cluster, sensorimotor cortex cluster, and cerebellum and peduncle cluster, demonstrated no significant differences between HIE males and females. In the perfusion comparison between male and female controls, there were no significant perfusion changes in those brain clusters. Brain perfusion in neonatal HIE differs between males and females in the thalamus, a metabolically active region within neonates, with males demonstrating lower perfusion. This difference in perfusion may reflect sex-related disparities in response to and recovery from hypoxic-ischaemic events.

Cerebral Pulsed Arterial Spin Labeling Perfusion Weighted Imaging Predicts Language and Motor Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy.

Rationale and Objectives: To compare cerebral pulsed arterial spin labeling (PASL) perfusion among controls, hypoxic ischemic encephalopathy (HIE) neonates with normal conventional MRI(HIE/MRI⊕), and HIE neonates with abnormal conventional MRI(HIE/MRI⊖). To create a predictive machine learning model of neurodevelopmental outcomes using cerebral PASL perfusion.Materials and Methods: A total of 73 full-term neonates were evaluated. The cerebral perfusion values were compared by permutation test to identify brain regions with significant perfusion changes among 18 controls, 40 HIE/MRI⊖ patients, and 15 HIE/MRI⊕ patients. A machine learning model was developed to predict neurodevelopmental outcomes using the averaged perfusion in those identified brain regions.Results: Significantly decreased PASL perfusion in HIE/MRI⊖ group, when compared with controls, were found in the anterior corona radiata, caudate, superior frontal gyrus, precentral gyrus. Both significantly increased and decreased cerebral perfusion changes were detected in HIE/MRI⊕ group, when compared with HIE/MRI⊖ group. There were no significant perfusion differences in the cerebellum, brainstem and deep structures of thalamus, putamen, and globus pallidus among the three groups. The machine learning model demonstrated significant correlation (p < 0.05) in predicting language(r = 0.48) and motor(r = 0.57) outcomes in HIE/MRI⊖ patients, and predicting language(r = 0.76), and motor(r = 0.53) outcomes in an additional group combining HIE/MRI⊖ and HIE/MRI⊕.Conclusion: Perfusion MRI can play an essential role in detecting HIE regardless of findings on conventional MRI and predicting language and motor outcomes in HIE survivors. The perfusion changes may also reveal important insights into the reperfusion response and intrinsic autoregulatory mechanisms. Our results suggest that perfusion imaging may be a useful adjunct to conventional MRI in the evaluation of HIE in clinical practice.

Characteristic Blood-Perfusion Reduction of Walker 256 Tumor Induced by Diagnostic Ultrasound and Microbubbles

Tumor angiogenesis is characterized by a defective, leaky and fragile microvascular construction, and microbubble-enhanced ultrasound (MEUS) with high-pressure amplitude is capable of disrupting tumor microvasculature and arresting blood perfusion. In this study, we tried to investigate whether the blood perfusion of a malignant tumor can be characteristically interrupted by combining microbubbles and diagnostic ultrasound (US). Twenty-nine Sprague-Dawley (SD) rats with subcutaneous Walker 256 tumors and seven healthy SD rats were included. Fifteen tumors were treated by MEUS, which combined constant microbubble injection and 20 episodes of irradiation by diagnostic US (i.e., acoustic radiation force impulse [ARFI] imaging). The other 14 tumors were treated by ARFI or sham US only. Seven skeleton muscles from healthy SD rats were also treated with MEUS, serving as the control. Contrast-enhanced ultrasound (CEUS) was performed before and after all treatments. The blood perfusion of the tumor MEUS group showed a significant drop immediately after treatment, followed by a quick, incomplete perfusion recovery within 10–20 min. The visual perfusion scoring result was consistent with the quantitative analysis by CEUS peak intensity. However, there were no significant perfusion changes in the tumor control groups or the muscle control group. Histologic examination found severe microvascular disruption and hemorrhage in the MEUS-treated tumors but not in the control groups. Therefore, the treatment combining diagnostic US and microbubbles can specifically decrease or interrupt the blood perfusion of Walker 256 tumors, which could be a potential new imaging method for diagnosing malignant tumors.

Radiologic-pathologic evidence of brain injury: hypoperfusion in the Papez circuit results in poor neurodevelopmental outcomes in neonatal hypoxic ischemic encephalopathy.

To provide radiologic-pathologic correlation of brain injury in the Papez circuit in hypoxic-ischemic encephalopathy (HIE) neonates and correlate radiologic findings with long-term neurodevelopmental outcomes. Twenty full-term HIE neonates were evaluated. Cerebral blood flow (CBF) values, obtained through pulsed arterial spin labeling (ASL) perfusion-weighted MRI, were compared by permutation test to identify brain regions with statistically significant perfusion changes between 14 HIE neonates without evidence of developmental delay by Bayley-III (mean age 8.2 ± 7.2days) and 6 HIE neonates with evidence of developmental delay (mean age 13.1 ± 8.0days). Four histopathologic studies on specimens were taken from post-mortem brains of another group of infants (mean age 10 ± 6.8days) with HIE. The infants were not the same ones who had MRIs. Significantly decreased perfusion in Papez circuit was found in HIE neonates with developmental delay compared with HIE neonates without delay. Decreased ASL perfusion values were seen in Papez circuit structures of the fornix (p = 0.002), entorhinal cortex (p = 0.048), amygdala (p = 0.036), hippocampus (p = 0.033), and thalamus (p = 0.036). In autopsy specimens of neonates with HIE, anoxic (eosinophilic) neurons, reactive astrocytes, and white matter rarefaction were observed in these regions, providing pathology correlation to the imaging findings of HIE. The Papez circuit is susceptible to hypoxic-ischemic injury in neonates as demonstrated by perfusion-weighted imaging and histopathology. This sheds new light onto a possible non-familial mechanism of neuropsychiatric disease evolution initiated in the infant period and raises the potential for early identification of at-risk children.

Non-Invasive Monitoring of Oxygen Tension and Oxygen Transport Inside Subcutaneous Devices After H2S Treatment

Medical devices for cell therapy can be improved through prevascularization. In this work we study the vascularization of a porous polymer device, previously used by our group for pancreatic islet transplantation with results indicating improved glycemic control. Oxygen partial pressure within such devices was monitored non-invasively using an optical technique. Oxygen-sensitive tubes were fabricated and placed inside devices prior to subcutaneous implantation in nude mice. We tested the hypothesis that vascularization will be enhanced by administration of the pro-angiogenic factor hydrogen sulfide (H2S). We found that oxygen dynamics were unique to each implant and that the administration of H2S does not result in significant changes in perfusion of the devices as compared with control. These observations suggest that vascular perfusion and density are not necessarily correlated, and that the rate of vascularization was not enhanced by the pro-angiogenic agent.

Multimodal PET/MRI Imaging Results Enable Monitoring the Side Effects of Radiation Therapy.

Radiotherapy is one of the most frequently applied treatments in oncology. Tissue-absorbed ionizing radiation damages not only targeted cells but the surrounding cells too. The consequent long-term induced oxidative stress, irreversible tissue damage, or second malignancies draw attention to the urgent need of a follow-up medical method by which personalized treatment could be attained and the actually dose-limiting organ could be monitored in the clinical practice. We worked out a special hemisphere irradiation technique for mice which mimics the radiation exposure during radiotherapy. We followed up the changes of possible brain imaging biomarkers of side effects, such as cerebral blood flow, vascular endothelial function, and cellular metabolic processes for 60 days. BALB/c mice were divided into two groups (n=6 per group) based on the irradiation doses (5 and 20 Gy). After the irradiation procedure arterial spin labeling (ASL), diffusion-weighted imaging (DWI) in magnetic resonance modality and [18F]fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) scans of the brain were obtained at several time points (3, 7, 30, and 60 days after the irradiation). Significant physiological changes were registered in the brain of animals following the irradiation by both applied doses. Elevated standard uptake values were detected all over the brain by FDG-PET studies 2 months after the irradiation. The apparent diffusion coefficients from DWI scans significantly decreased one month after the irradiation procedure, while ASL studies did not show any significant perfusion changes in the brain. Altogether, our sensitive multimodal imaging protocol seems to be an appropriate method for follow-up of the health status after radiation therapy. The presented approach makes possible parallel screening of healthy tissues and the effectiveness of tumor therapy without any additional radiation exposure.

Photoplethysmography for blood volumes and oxygenation changes during intermittent vascular occlusions

Photoplethysmography (PPG) is an optical technique that measures blood volume variations. The main application of dual-wavelength PPG is pulse oximetry, in which the arterial oxygen saturation (SpO_2) is calculated noninvasively. However, the PPG waveform contains other significant physiological information that can be used in conjunction to SpO_2 for the assessment of oxygenation and blood volumes changes. This paper investigates the use of near infrared spectroscopy (NIRS) processing techniques for extracting relative concentration changes of oxygenated (DeltaHbO_2), reduced (DeltaHHb) and total haemoglobin (DeltatHb) from dual-wavelength PPG signals during intermittent pressure-increasing vascular occlusions. A reflectance PPG sensor was attached on the left forearm of nineteen (n = 19) volunteers, along with a reference NIRS sensor positioned on the same forearm, above the left brachioradialis. The investigation protocol consisted of seven intermittent and pressure-increasing vascular occlusions. Relative changes in haemoglobin concentrations were obtained by applying the modified Beer–Lambert law to PPG signals, while oxygenation changes were estimated by the difference between red and infrared attenuations of DC PPGs (A_{Ox} = DeltaA_{IR} − DeltaA_R) and by the conventional SpO_2. The DeltaHbO_2, DeltaHHb, DeltatHb from the PPG signals indicated significant changes in perfusion induced by either partial and complete occlusions (p < 0.05). The trends in the variables extracted from PPG showed good correlation with the same parameters measured by the reference NIRS monitor. Bland and Altman analysis of agreement between PPG and NIRS showed underestimation of the magnitude of changes by the PPG. A_{Ox} indicated significant changes for occlusion pressures exceeding 20 mmHg (p < 0.05) and correlation with tissue oxygenation changes measured by NIRS, while SpO_2 had significant changes after 40 mmHg (p < 0.05). Relative changes in haemoglobin concentrations can be estimated from PPG signals and they showed a good level of accuracy in the detection of perfusion and oxygenation changes induced by different degrees of intermittent vascular occlusions. These results can open up to new applications of the PPG waveform in the detection of blood volumes and oxygenation changes.

Detection of liver micrometastases from colorectal origin by perfusion CT in a rat model

Some patients with colorectal carcinoma have liver metastases (LMs) which cannot be detected by conventional imaging. This study aimed to assess whether hepatic perfusion changes induced by micrometastases can be detected by perfusion computed tomography (CT). LMs were produced in rats by injecting carcinoma cells into the portal vein. Perfusion CT was performed at microscopic (day 10), interval (day 17), and macroscopic stage (day 34). Perfusion parameters were computed using a dual-input one-compartmental model. Micro and macro LMs presented a mean diameter of 0.5 and 2.6 mm, respectively. Compared to controls, LMs at interval (1.1 mm) and macroscopic stage induced significant perfusion changes: a decrease of 42% (P=0.004) and 41% (P=0.029) in hepatic transit time and an increase of 292% (P=0.073) and 240% (P=0.001) in portal delay, respectively. LMs with a mean diameter between 1.1 and 2.6 mm induced significant hepatic perfusion changes, detected by CT. Such detection may help to select patients and propose chemotherapy at the time of primary tumor resection.

A mathematical model of the metabolic and perfusion effects on cortical spreading depression.

Cortical spreading depression (CSD) is a slow-moving ionic and metabolic disturbance that propagates in cortical brain tissue. In addition to massive cellular depolarizations, CSD also involves significant changes in perfusion and metabolism—aspects of CSD that had not been modeled and are important to traumatic brain injury, subarachnoid hemorrhage, stroke, and migraine. In this study, we develop a mathematical model for CSD where we focus on modeling the features essential to understanding the implications of neurovascular coupling during CSD. In our model, the sodium-potassium–ATPase, mainly responsible for ionic homeostasis and active during CSD, operates at a rate that is dependent on the supply of oxygen. The supply of oxygen is determined by modeling blood flow through a lumped vascular tree with an effective local vessel radius that is controlled by the extracellular potassium concentration. We show that during CSD, the metabolic demands of the cortex exceed the physiological limits placed on oxygen delivery, regardless of vascular constriction or dilation. However, vasoconstriction and vasodilation play important roles in the propagation of CSD and its recovery. Our model replicates the qualitative and quantitative behavior of CSD—vasoconstriction, oxygen depletion, extracellular potassium elevation, prolonged depolarization—found in experimental studies. We predict faster, longer duration CSD in vivo than in vitro due to the contribution of the vasculature. Our results also help explain some of the variability of CSD between species and even within the same animal. These results have clinical and translational implications, as they allow for more precise in vitro, in vivo, and in silico exploration of a phenomenon broadly relevant to neurological disease.

A: AORTIC STENOSIS: QUANTIFICATION OF DIFFUSE FIBROSIS, EXAMINATION OF MYOCARDIAL PHYSIOLOGY AND RESPONSE TO RAMIPRIL

<h3>Introduction</h3> The physiological response of the myocardium to pressure overload is important in determining outcome in aortic stenosis (AS). It may be modified by inhibition of the renin-angiotensin system. We used cardiac magnetic resonance (CMR) to assess diffuse myocardial fibrosis (DMF), myocardial physiology and the response to Rampril in AS. <h3>Methods</h3> <i>DMF in AS</i> 24 symptomatic patients with severe AS underwent myocardial biopsy at the time of aortic valve replacement (AVR). 85 asymptomatic AS patients and 33 matched controls were recruited. All subjects underwent CMR scanning at 1.5 for T1 mapping. <i>Myocardial physiology in moderate AS</i> 31 patients with moderate asymptomatic AS and 12 matched normal controls underwent CMR scanning at 1.5 T for measurement of strain, perfusion and T1 values. <i>Ramipril in Asymptomatic AS</i> A double-blinded, placebo-controlled, randomized, prospective trial was carried out. 100 patients with moderate or severe asymptomatic AS and normal LV function were randomized to Ramipril 10 mg od (n=50) or placebo (n=50) for a year. 95 patients underwent CMR scanning (LV mass, function, strain, perfusion, T1 mapping), echocardiography and exercise testing at 0, 6 and 12 months. <h3>Results</h3> <i>DMF in AS</i> There was a significant correlation between CMR T1 values and collagen vascular fraction (CVF)% (r=0.65, p=0.002) from biopsy. Mean T1 values were significantly longer in all groups with severe AS (972±33 ms in severe asymptomatic, 1014 ±38 ms in severe symptomatic) than in normal controls (944±16 ms) (p&lt;0.05) (Figure&nbsp;1). The strongest associations with T1 values were for aortic valve area (r=−0.40, p=0.001) and left ventricular mass index (LVMI) (r=0.36, p=0.008). <i>Myocardial physiology in moderate AS</i> There was a significant reduction in perfusion and longitudinal strain (LS) in moderate AS patients compared to normals; myocardial perfusion index 1.9±0.2 in normals, 1.3±0.4 in AS and LS -15±1 in normals, -11±2 in AS. (both p&lt;0.001). There was a moderate correlation between LS and perfusion (r=-0.4 p&lt;0.05). <i>Ramipril in Asymptomatic AS</i> Data was available in 78 patients for the primary endpoint (LV mass) at 12 months. There was reduction in LV mass in the Ramipril compared to placebo group; −3.96g (CI: −8.55, 0.62) p=0.089 at 6 months and −8.36g (CI:−14.22, −2.51) p=0.006 at 12 months. Figure&nbsp;2. There was a trend towards reduction in valve area (p=0.067), peak aortic velocity (p=0.056) and fewer deaths in the Ramipril group after completion of the trial (p= 0.074). <h3>Conclusion</h3> DMF in AS may be assessed noninvasively using CMR. DMF increases with severity of the AS and LV hypertrophy. Significant changes in perfusion and LS already exist in moderate AS, indicating that significant myocardial changes occur early in the disease process. Rampril 10 mg over a year led to a significant reduction in LV mass in the treated group. A larger multi-centre clinical outcome trial is required to determine whether this translates into clinical benefit.

Intravenous aflibercept administered in combination with irinotecan, 5-fluorouracil and leucovorin in patients with advanced solid tumours: Results from the expansion cohort of a phase I study

BackgroundFollowing the dose-escalation stage, this double-blind expansion stage of the phase I study evaluated the safety, pharmacodynamics, pharmacokinetics, anti-vascular effects and antitumour activity of aflibercept 4mg/kg with irinotecan, 5-fluorouracil and leucovorin (LV5FU2). Patients and methodsPatients with advanced solid tumours were randomised at cycle-1 to placebo or aflibercept (4mg/kg) on day 1 then irinotecan–LV5FU2 on days 1 and 2. Subsequently, all patients received aflibercept with irinotecan–LV5FU2 every 2weeks. Anti-vascular effects were assessed using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). ResultsTwenty-seven patients were treated; 14 received placebo in cycle-1 followed by aflibercept in later cycles and 13 received aflibercept 4mg/kg upfront. The median number of aflibercept cycles was 16 (range 1–44), 12 patients received ⩾20 cycles. Most frequent grade 3/4 adverse events were neutropenia (37%), fatigue (33%) and hypertension (30%). No anti-aflibercept antibodies were detected. Four patients achieved partial responses and 17 had stable disease, lasting >3months in 14 patients. Plasma levels of free over vascular endothelial growth factor-bound aflibercept were adequate, with steady-state achieved from cycle-3. Exploratory DCE-MRI showed no significant perfusion changes with aflibercept. ConclusionAflibercept 4mg/kg plus irinotecan–LV5FU2 every 2weeks had acceptable toxicity and pharmacokinetics, and showed promising antitumour activity.

Abstract 3013: Cerebral Perfusion Parameter Differences in Clinically Relevant Categories of Carotid Stenosis/Occlusion.

Hypothesis: To determine whether clinically relevant categories of carotid stenosis are associated with changes in cerebral blood flow. Methods: We examined a consecutive cohort of stroke patients with confirmed stroke on DWI imaging who underwent CT angiography (CTA) and perfusion CT imaging on presentation with acute symptoms. Degree of carotid stenosis was measured per NASCET criteria on CTA. Perfusion CT was analyzed to calculate relative mean transit time (rMTT), relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) of normal brain tissue ipsilateral to carotid disease. Measurements excluded areas of infarction to avoid confounding hemispheric perfusion changes with local changes due to distal cerebral artery occlusion(s), and subjects with MCA occlusions on any side were excluded. Results: The cohort consisted of 119 patients. Of these 8.4% had 100% ipsilateral carotid occlusion, 1.7% had near-occlusion, 5% had 70-99% stenosis, 5.9% had 50-69% stenosis, and 79% had &lt;50% stenosis. Subjects with 100% carotid occlusion had a higher rMTT (median 1.503, IQR 0.974 to 2.44; p=0.02) when compared to the expected normal rMTT of 1.0. These patients also had a lower rCBF (median 0.708, IQR 0.553 to 1.116; p=0.048) when compared to the expected normal rCBF of 1.0. Perfusion parameters of subjects with carotid near-occlusion did not differ significantly from the expected normal values. Subjects with 70-99% stenosis had slightly higher rMTT (median 1.246, IQR 1.034 to 1.422; p=0.031) and slightly higher rCBV (median 1.088, IQR 1.046 to 1.142; p=0.031) when compared to the expected normal of 1.0. Subjects with 50-69% carotid stenosis and &lt;50% stenosis did not have significantly different perfusion parameters when compared to expected normal values. Conclusions: This is the first reported correlation between clinically relevant categories of carotid stenosis and perfusion parameters measured by perfusion CT imaging of the brain. Subjects with 100% occlusion appeared to have hemodynamically significant changes in perfusion (increased rMTT by ∼50%, decreased rCBF by ∼30%). Patients with 70-99% stenosis had less pronounced changes in rMTT, and no change in rCBF. Interestingly, patients with carotid near-occlusion showed no significant change in perfusion parameters, suggesting that this subgroup of patients may have developed sufficient collateral circulation. Patients with 0-69% stenosis had no significant changes in perfusion parameters. These findings may have significant implications in our approach to patients with carotid occlusion/stenosis and need to be confirmed in larger patient populations.

Rapid intravenous infusion of 20mL/kg saline alters the distribution of perfusion in healthy supine humans

Rapid intravenous saline infusion, a model meant to replicate the initial changes leading to pulmonary interstitial edema, increases pulmonary arterial pressure in humans. We hypothesized that this would alter lung perfusion distribution. Six healthy subjects (29 ± 6 years) underwent magnetic resonance imaging to quantify perfusion using arterial spin labeling. Regional proton density was measured using a fast-gradient echo sequence, allowing blood delivered to the slice to be normalized for density and quantified in mL/min/g. Contributions from flow in large conduit vessels were minimized using a flow cutoff value (blood delivered > 35% maximum in mL/min/cm(3)) in order to obtain an estimate of blood delivered to the capillary bed (perfusion). Images were acquired supine at baseline, after infusion of 20 mL/kg saline, and after a short upright recovery period for a single sagittal slice in the right lung during breath-holds at functional residual capacity. Thoracic fluid content measured by impedance cardiography was elevated post-infusion by up to 13% (p<0.0001). Forced expiratory volume in 1s was reduced by 5.1% post-20 mL/kg (p=0.007). Infusion increased perfusion in nondependent lung by up to 16% (6.4 ± 1.6 mL/min/g baseline, 7.3 ± 1.8 post, 7.4 ± 1.7 recovery, p=0.03). Including conduit vessels, blood delivered in dependent lung was unchanged post-infusion; however, was increased at recovery (9.4 ± 2.7 mL/min/g baseline, 9.7 ± 2.0 post, 11.3 ± 2.2 recovery, p=0.01). After accounting for changes in conduit vessels, there were no significant changes in perfusion in dependent lung following infusion (7.8 ± 1.9 mL/min/g baseline, 7.9 ± 2.0 post, 8.5 ± 2.1 recovery, p=0.36). There were no significant changes in lung density. These data suggest that saline infusion increased perfusion to nondependent lung, consistent with an increase in intravascular pressures. Dependent lung may have been "protected" from increases in perfusion following infusion due to gravitational compression of the pulmonary vasculature.

Alteration of Ictal and Interictal Perfusion in Patients with Paroxysmal Kinesigenic Dyskinesia

Although previous cerebral blood flow studies have suggested that the basal ganglia or thalamus are involved in the pathogenesis of paroxysmal kinesigenic dyskinesia (PKD), the precise anatomic substrate or pathophysiological networks associated with PKD remain unclear. Here, ictal and interictal single photon emission computed tomography (SPECT) in 2 patients with idiopathic PKD compared to 6 age-matched normal controls and the perfusion findings of subtraction ictal SPECT co-registered to MRI (SISCOM) in 1 patient are reported. The interictal and ictal perfusion changes were different in each of the patients and there were no consistent anatomic substrates observed. 2 patients had significant perfusion changes in the left frontal/temporal cortices compared to controls, whereas the others showed an increased uptake of 99mTc-ethyl cysteinate dimer (ECD) in the left occipital area on subtraction SPECT imaging. The results of this study suggest that the pathophysiology of PKD cannot be simply explained by lesions of the basal ganglia or thalamus, and that other associated areas of the cortex are likely involved in these movement disorders.

Four‐dimensional transcatheter intraarterial perfusion MRI monitoring of radiofrequency ablation of rabbit VX2 liver tumors

To investigate the hypothesis that four-dimensional (4D) transcatheter intraarterial perfusion (TRIP) magnetic resonance imaging (MRI) can quantify immediate perfusion changes after radiofrequency (RF) ablation in rabbit VX2 liver tumors. Nine New Zealand White rabbits were used to surgically implant VX2 liver tumors. During ultrasound-guided RF ablation, tumors received either a true or sham ablation. After selective catheterization of the left hepatic artery under x-ray fluoroscopy, we acquired pre- and post-RF ablation 4D TRIP MR images using 3 mL of 2.5% intraarterial gadopentetate dimeglumine. Two regions-of-interest were drawn upon each tumor to generate signal-intensity time curves. Area under the curve (AUC) was calculated to provide semiquantitative perfusion measurements that were compared using a paired t-test (α = 0.05). Ablated tissue was visually confirmed on pathology using Evans blue dye. Mean AUC perfusion of VX2 tumors for the true ablation group decreased by 92.0% (95% confidence interval [CI]: 83.3%-100%), from 1913 (95% CI: 1557, 2269) before RF ablation to 76.6 (95% CI: 18.4, 134.8) after RF ablation (a.u., P < 0.001). Sham-ablated tumors demonstrated no significant perfusion changes. 4D TRIP MRI can quantify liver tumor perfusion reductions in VX2 rabbits after RF ablation. This MRI technique can potentially be used to improve tumor response assessment at the time of RF ablation.