Perfusion Studies Research Articles

Sodium-Glucose Cotransporter-2 Inhibition Normalizes Metabolic Derangements in the Ischemic Myocardium

IntroductionSodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown efficacy in the context of heart failure but have not been well-studied in ischemic heart disease. We employed a large animal model of chronic coronary artery disease and metabolic syndrome (MS) to investigate the hemodynamic and metabolic consequences of SGLT2i administration. MethodsThirty-eight Yorkshire swine were divided into two groups, with half (n = 21) receiving a high fat diet to induce MS, and the other half fed a standard diet (n = 17). All animals underwent thoracotomy for ameroid constrictor placement over the left circumflex coronary artery. Treatment with SGLT2i was then initiated, generating four groups: regular diet placebo (CON, n = 9), regular diet canagliflozin (n = 8), high-fat control (n = 11), and high-fat canagliflozin (n = 10). After 5 wks, all animals underwent terminal myocardial harvest with pressure-volume loop acquisition, perfusion studies, and tissue resection for molecular analysis. ResultsSGLT2i improved multiple measures of myocardial performance, including a nearly 1.5-fold increase in both cardiac output and ejection fraction; these changes were associated with augmented capillary density and a twofold increase perfusion to the ischemic myocardium. These augmentations were blunted; however, in the presence of MS, and associated with modulated myocardial expression of multiple major metabolic enzymes. ConclusionsSGLT2i significantly improved cardiac function in our large animal model of coronary artery disease, with metabolic modulation of the myocardial tissue serving as a candidate account of these changes. The blunting seen with MS underscores the dependence of clinical translatability on faithful representation of the biochemical environment of human disease.

The role of stress echocardiography in patients with congenital abnormalities of coronary arteries: two tertiary cardiac centres experience

Abstract Background Coronary anomalies (CA) include anomalous aortic origin of a coronary artery (AAOCA), anomalous coronary artery from the pulmonary artery and coronary fistulae. While outcome of natural history of anomalous left coronary artery from the pulmonary artery (ALCAPA) is poor, assessment of stress-induced ischaemia and/or arrhythmia are warranted for clinical decision making in AAOCA. Purpose The aim of this study was to establish the prevalence of ischaemia during exercise stress echocardiography (ESE) in patients with different congenital CA. Methods Patients with CA who had stress exercise echocardiography from two large tertiary cardiac centres were retrospectively recruited. Treadmill/bike exercise stress echo tests were performed and analysed according to ESC guidelines. Computed tomography (CT), magnetic resonance imaging (MRI), myocardial perfusion scintigraphy, positron emission tomography (PET) and invasive angiogram with intravascular ultrasound (IVUS) were used for CA morphology and myocardial perfusion assessment. Patients with sclerotic stenosis of >50% in any of the coronary arteries were excluded from this study. Results Total 59 patients, including 8 ALCAPA, 4 coronary fistula and 47 AAOCA (12 anomalous aortic origin of the left coronary artery (AAOLCA) and 35 anomalous aortic origin of the right coronary artery (AAORCA)) formed the study cohort. The mean age was 44±17 years. Cardiac symptoms at rest were present in 5 (63%) ALCAPA, 31 (66%) patients with with AAOCA, and none in patients with coronary fistula. Nine patients (7 ALCAPA, 1 coronary fistula and 1 AAOLCA) had undergone previous repair. Out of 47 patients with AAOCA patients, 31 (66%) had interarterial course of coronary arteries, and 8 (17%) had intramural course. A positive ESE presents in 2 (25%) ALCAPA, 1 (25%) coronary fistula patient and 1 (2%) AAOCA patient. Myocardial perfusion was assessed in 12 of 59 (20%) patients, of which 9 were AAOCA. Myocardial perfusion studies were negative in 11 patients with negative ESE tests, while only in one patient with AAOLCA myocardial perfusion defects were found on MRI and PET despite negative ESE. No major adverse cardiovascular events were observed during follow-up of patients with negative ESE. Following ESE, surgical repair of CA has been performed in 3 patients with AAORCA and in 2 patients with AAOLCA based on either symptoms attributable to anomalous coronary, evidence of myocardial ischaemia on myocardial perfusion assessment or high-risk anatomy.While 4 out of 5 repaired patients were symptomatic before repair, they became asymptomatic following repair. Conclusions Incidence of ischaemia on exercise stress echo is extremely low in AAOCA patients despite symptoms at rest and malignant anatomical features. Improving stress echo methodology by using myocardial perfusion assessment might shed a light on this discrepancy between ESE results and symptomatic status/high-risk anatomy.

L-Arginine and asymmetric dimethylarginine (ADMA) transport across the mouse blood-brain and blood-CSF barriers: Evidence of saturable transport at both interfaces and CNS to blood efflux

L-Arginine is the physiological substrate for the nitric oxide synthase (NOS) family, which synthesises nitric oxide (NO) in endothelial and neuronal cells. NO synthesis can be inhibited by endogenous asymmetric dimethylarginine (ADMA). NO has explicit roles in cellular signalling and vasodilation. Impaired NO bioavailability represents the central feature of endothelial dysfunction associated with vascular diseases. Interestingly, dietary supplementation with L-arginine has been shown to alleviate endothelial dysfunctions caused by impaired NO synthesis. In this study the transport kinetics of [3H]-arginine and [3H]-ADMA into the central nervous system (CNS) were investigated using physicochemical assessment and the in situ brain/choroid plexus perfusion technique in anesthetized mice. Results indicated that L-arginine and ADMA are tripolar cationic amino acids and have a gross charge at pH 7.4 of 0.981. L-Arginine (0.00149±0.00016) has a lower lipophilicity than ADMA (0.00226±0.00006) as measured using octanol-saline partition coefficients. The in situ perfusion studies revealed that [3H]-arginine and [3H]-ADMA can cross the blood-brain barrier (BBB) and the blood-CSF barrier. [3H]-Arginine (11.6nM) and [3H]-ADMA (62.5nM) having unidirectional transfer constants (Kin) into the frontal cortex of 5.84±0.86 and 2.49±0.35 μl.min-1.g-1, respectively, and into the CSF of 1.08±0.24 and 2.70±0.90 μl.min-1.g-1, respectively. In addition, multiple-time uptake studies revealed the presence of CNS-to-blood efflux of ADMA. Self- and cross-inhibition studies indicated the presence of transporters at the BBB and the blood-CSF barriers for both amino acids, which were shared to some degree. Importantly, these results are the first to demonstrate: (i) saturable transport of [3H]-ADMA at the blood-CSF barrier (choroid plexus) and (ii) a significant CNS to blood efflux of [3H]-ADMA. Our results suggest that the arginine paradox, in other words the clinical observation that NO-deficient patients respond well to oral supplementation with L-arginine even though the plasma concentration is sufficient to saturate endothelial NOS, could be related to altered ADMA transport (efflux).

Effects of Genipin Crosslinking of Porcine Perilimbal Sclera on Mechanical Properties and Intraocular Pressure.

The mechanical properties of sclera play an important role in ocular functions, protection, and disease. Modulating the sclera's properties by exogenous crosslinking offers a way to expand the tissue's range of properties for study of the possible influences on the eye's behavior and diseases such as glaucoma and myopia. The focus of this work was to evaluate the effects of genipin crosslinking targeting the porcine perilimbal sclera (PLS) since the stiffness of this tissue was previously found in a number of studies to influence the eye's intraocular pressure (IOP). The work includes experiments on tensile test specimens and whole globes. The specimen tests showed decreased strain-rate dependence and increased relaxation stress due to the cross-linker. Whole globe perfusion experiments demonstrated that eyes treated with genipin in the perilimbal region had increased IOPs compared to the control globes. Migration of the cross-linker from the target tissue to other tissues is a confounding factor in whole globe, biomechanical measurements, with crosslinking. A novel quantitative genipin assay of the trabecular meshwork (TM) was developed to exclude globes where the TM was inadvertently crosslinked. The perfusion study, therefore, suggests that elevated stiffness of the PLS can significantly increase IOP apart from effects of the TM in the porcine eye. These results demonstrate the importance of PLS biomechanics in aqueous outflow regulation and support additional investigations into the distal outflow pathways as a key source of outflow resistance.

Current opinion: antiretrovirals during pregnancy and breastfeeding

Purpose of review To review the most important literature from the past 2 years on the pharmacokinetics of antiretrovirals in pregnancy, placental transfer, and breastmilk. Recent findings Concentrations of antiretrovirals frequently used in pregnancy and their placental transfer are described, together with infant exposure through breastmilk. Also, applications of ex-vivo and in-silico studies, such as placenta perfusion studies and PBPK models, are discussed. Summary Great efforts were made in the past 2 years to accelerate the availability of data on antiretrovirals during pregnancy and lactation. Bictegravir showed decreased but still sufficient concentrations during pregnancy, leading to a label change by the FDA. In-silico and clinical studies on long-acting cabotegravir and rilpivirine generated information leading to cautious use of these formulations in pregnancy. Low infant exposure to antiretrovirals through breastmilk is expected for most compounds. Despite the impact of these studies, more incentives are needed for earlier implementation, for instance, during the developmental phase of drugs, to provide women antenatally with proper information on their drugs.

In situ Single-Pass Perfused Rabbit Intestinal Study sample Analysis of Ractopamine by UPLC

In recent years, the prediction of oral drug absorption in humans has been a challenge for researchers and many techniques for permeability studies have been developed for several purposes, including biowaiver processes. The Single-Pass Intestinal Perfusion (SPIP) method performed in rats can provide permeability results closest to in vivo condition. he use of SPIP in rats and calculations for absorption prediction in humans may indicate the transport mechanisms and/or pre-systemic metabolism involved on permeation processes of drugs, since this model is the closest to in vivo conditions. Ractopamine hydrochloride is a commercial beta-adrenergic agonist commonly used as a dietary supplement in cattle production for improved feed efficiency and growth promotion. Currently, regulatory target tissues (as approved in the New Animal Drug Application with Food and Drug Administration) for ractopamine residue testing are muscle and liver. The aim of the study is to develop and validate an UPLC assay method to determine whether detectable and quantifiable levels of perfused ractopamine in small intestine of cattle or not. The separation is carried on Acquity UPLC BEH C18 (150mm x 2.1mm, 1.7 µm) reversed phase column using acetonitrile and 0.01M ammonium formate as the mobile phase in gradient mode at flow rate of 0.5mL/min. The precision, accuracy, extraction recovery, matrix effect, and stability meet the requirements of the guiding principles. In order to verify the sensitivity and selectivity of the method in a real-time situation, the developed method is successfully applied to a perfusion study in small intestine of rabbit and the samples were analyzed by Empower software.

CT perfusion to measure venous outflow in acute ischemic stroke in patients with a large vessel occlusion

BackgroundRobust venous outflow (VO) profiles, measured by degree of venous opacification on pre-thrombectomy CT angiography (CTA) studies, are strongly correlated with favorable outcomes in patients with large vessel occlusion acute...

How anatomical impairments found on CT affect perfusion percentage assessed by SPECT/CT scan?

CT images can identify structural and opacity alterations of the lungs while nuclear medicine's lung perfusion studies show the homogeneity (or lack of) of blood perfusion on the organ. Therefore, the use of SPECT/CT in lung perfusion scintigraphies can help physicians to assess anatomical and functional alterations of the lungs and to differentiate between acute and chronic disease. To develop a computer-aided methodology to quantify the total global perfusion of the lungs via SPECT/CT images and to compare these results with parenchymal alterations obtained in CT images. 39 perfusion SPECT/CT images collected retrospectively from the Nuclear Medicine Facility of Botucatu Medical School's Clinics Hospital in São Paulo, Brazil, were analyzed. Anatomical lung impairments (emphysema, collapsed and infiltrated tissue) and the functional percentage of the lungs (blood perfusion) were quantified from CT and SPECT images, with the aid of the free, open-source software 3D Slicer. The results obtained with 3D Slicer (3D-TGP) were also compared to the total global perfusion of each patient's found on their medical report, obtained from visual inspection of planar images (2D-TGP). This research developed a novel and practical methodology for obtaining lungs' total global perfusion from SPECT/CT images in a semiautomatic manner. 3D-TGP versus 2D-TGP showed a bias of 7% with a variation up to 67% between the two methods. Perfusion percentage showed a weak positive correlation with infiltration (p = 0.0070 and ρ = 0.43) and collapsed parenchyma (p = 0.040 and ρ = 0.33). This research brings meaningful contributions to the scientific community because it used a free open-source software to quantify the lungs blood perfusion via SPECT/CT images and pointed that the relationship between parenchyma alterations and the organ's perfusion capability might not be so direct, given compensatory mechanisms.

Tissue-Based Predictors of Impaired Right Ventricular Strain in Coronary Artery Disease: A Multicenter Stress Perfusion Study.

Right ventricular (RV) dysfunction is known to impact prognosis, but its determinants in coronary artery disease are poorly understood. Stress cardiac magnetic resonance (CMR) has been used to assess ischemia and infarction in relation to the left ventricle (LV); the impact of myocardial tissue properties on RV function is unknown. Vasodilator stress CMR was performed in patients with known coronary artery disease at 7 sites between May 2005 and October 2018. Myocardial infarction was identified on late gadolinium enhancement-CMR, and infarct transmurality was graded on a per-segment basis. Ischemia was assessed on stress CMR based on first-pass perfusion and localized by using segment partitions corresponding to cine and late gadolinium enhancement analyses. RV function was evaluated by CMR-feature tracking for primary analysis with a global longitudinal strain threshold of 20% used to define impaired RV strain (RVIS); secondary functional analysis via RV ejection fraction was also performed. A total of 2604 patients were studied, among whom RVIS was present in 461 patients (18%). The presence and magnitude of RVIS were strongly associated with LV dysfunction, irrespective of whether measured by LV ejection fraction or wall motion score (P<0.001 for all). Regarding tissue substrate, regions of ischemic and dysfunctional myocardium (ie, hibernating myocardium) and infarct size were each independently associated with RVIS (both P<0.001). During follow-up (median, 4.62 [interquartile range, 2.15-7.67] years), 555 deaths (21%) occurred. Kaplan-Meier analysis for patients stratified by presence and magnitude of RV dysfunction by global longitudinal strain and RV ejection fraction each demonstrated strong prognostic utility for all-cause mortality (P<0.001). RVIS conferred increased mortality risk (hazard ratio, 1.35 [95% CI, 1.11-1.66]; P=0.003) even after controlling for LV function, infarction, and ischemia. RVIS in patients with known coronary artery disease is associated with potentially reversible LV processes, including LV functional impairment due to ischemic and predominantly viable myocardium, which confers increased mortality risk independent of LV function and tissue substrate.

Artificial Trabecular Meshwork Structure Combining Melt Electrowriting and Solution Electrospinning.

The human trabecular meshwork (HTM) is responsible for regulating intraocular pressure (IOP) by means of gradient porosity. Changes in its physical properties, like increases in stiffness or alterations in the extracellular matrix (ECM), are associated with increases in the IOP, which is the primary cause of glaucoma. The complexity of its structure limits the engineered models to one-layered and simple approaches, which do not accurately replicate the biological and physiological cues related to glaucoma. Here, a combination of melt electrowriting (MEW) and solution electrospinning (SE) is explored as a biofabrication technique used to produce a gradient porous scaffold that mimics the multi-layered structure of the native HTM. Polycaprolactone (PCL) constructs with a height of 20-710 µm and fiber diameters of 0.7-37.5 µm were fabricated. After mechanical characterization, primary human trabecular meshwork cells (HTMCs) were seeded over the scaffolds within the subsequent 14-21 days. In order to validate the system's responsiveness, cells were treated with dexamethasone (Dex) and the rho inhibitor Netarsudil (Net). Scanning electron microscopy and immunochemistry staining were performed to evaluate the expected morphological changes caused by the drugs. Cells in the engineered membranes exhibited an HTMC-like morphology and a correct drug response. Although this work demonstrates the utility of combining MEW and SE in reconstructing complex morphological features like the HTM, new geometries and dimensions should be tested, and future works need to be directed towards perfusion studies.

Neuro-microcirculatory interrelationships in patients with kyphoscoliosis associated with neurological deficits

Background: The use of laser Doppler flowmetry with spectral wavelet analysis of blood flow fluctuations allows us to assess the functional state of thin unmyelinated nerve fibers and objectify the dynamics of recovery processes in patients with kyphoscoliotic spinal deformities associated with spinal cord compression. AIM: To study the features of neuromicrocirculatory relationships in patients with kyphoscoliosis associated with neurological deficits before and after surgical treatment. MATERIALS AND METHODS: 20 patients with spinal deformities associated with neurological deficits of varying severity were examined using the LDF method and operated on. Patients were examined before surgery, 1–2 weeks after surgery following regression of acute postoperative pain syndrome, 3–6 months, 6–12 months, and more than a year after surgery. The scope of the study included a general examination with a detailed assessment of the neurological status, radiation diagnostics (postural radiographs of the spine, computed tomography and magnetic resonance imaging of the spine with assessment of spinal canal stenosis). Patients with severe kyphoscoliotic deformities underwent CT myelography followed by the design of individual full-size 3D plastic models of the spine and myeloradicular structures. LDF with wavelet analysis was carried out at all periods of the survey. A perfusion study with determination of the average microcirculation was carried out at the level of the pad of the distal phalanx of the big toe using a two-channel LAKK-02 device with a semiconductor laser (sensing in the red Raman and infrared IR channels). The obtained LDF results were processed by spectral amplitude-frequency wavelet analysis to characterize microcirculation regulation factors in the ranges of sympathetic adrenergic regulation (0.02–0.046 Hz), sensory peptidergic influences (0.047–0.069 Hz), myogenic oscillations (0.07–0.145 Hz). RESULTS: After surgery, the activity of trophotropic sensory peptidergic nerve fibers, the values of perfusion of the microcirculatory channel increased and was maintained starting from the early postoperative period. Ergotropic sympathetic adrenergic activity was significantly decreased in the period of 6-12 months after surgery. Maximum mobilization of trophotropic neurogenic mechanisms of sanogenesis was observed in the period of 6-12 months after surgery. CONCLUSION: The obtained data indicate a significant participation of thin nerve fibers in the recovery processes after decompressive surgeries in the spinal canal zone and the creation of anatomical conditions for neurophysiological repair at the spinal cord level. The use of the LDF method with spectral wavelet analysis of blood flow fluctuations makes it possible to objectify the dynamics of thin unmyelinated nerve fibers and recovery processes in patients with kyphoscoliotic deformities of the spine associated with spinal cord compression.

Protocol description and initial experience in kidney graft perfusion using infrared thermography.

Protocol description for renal perfusion study using thermographic technology and description of the thermographic and clinical behavior of the transplanted kidneys before and after unclamping. Infrared thermographic images of renal grafts are obtained before kidney reperfusion, 10min after and just before closing the surgical wound. Thermographic data is evaluated together with the type of graft and donor, cold ischemia time, hypovascularized areas determined by the surgeon during surgical intervention, alterations in vascular flow in postoperative echo-Doppler, time at the beginning of graft function and serum creatinine monitoring during postoperative follow-up. 17 grafts were studied. The mean temperature of the grafts before reperfusion, 10min after and at the end of the surgery were 18.7°C (SD 6.27), 32.36°C (SD1.47) and 32.07°C (SD1.78) respectively. 4 grafts presented hypoperfused areas after reperfusion. These areas presented a lower temperature compared to the well perfused parenchyma surface using thermographic images. The study of the usefulness and applicability of thermography can allow the development of tools that provide additional objective information on organ perfusion in real time and non-invasive manner. Our protocol and initial results can contribute to provide new evidence. Further analyses should be developed to shed light on the role of this technology.

A Fatal Case of Powassan Virus Encephalitis

The Powassan virus (POWV) is part of the Flaviviridae family. It is mainly transmitted via tickbite but can rarely be spread person-to-person through blood transfusions. Initial symptoms include fever, headache, and vomiting. It can cause severe symptoms, including confusion, aphasia, and seizures. Approximately 1 out of 10 people with severe disease die. From 2010 to 2020, 194 Powassan virus cases have been reported to the Center for Disease Control (CDC), with 22 of them resulting in death. In this case report, we discuss a 39-year-old female who presented with fever, myalgia, and confusion. During her hospitalization, she developed tonic-clonic seizures, which required sedation and intubation. A central venous catheter was inserted due to poor intravenous access, and in the process of placing it, the provider sustained a needle stick injury. The patient was eventually diagnosed with POWV encephalitis and transferred to a higher level of care, where a brain perfusion study showed an absence of brain flow consistent with brain death. After a discussion with the family, the decision was made to extubate the patient terminally. The provider who sustained the needle stick injury reported no concerning symptoms two years after the event.

Pulmonary transit time is a predictor of outcomes in heart failure: a cardiovascular magnetic resonance first-pass perfusion study

BackgroundPulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure.MethodsWe recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF) < 50% on referral echocardiogram. Patients were followed up by a review of medical records for major adverse cardiovascular events (MACE) defined as all-cause mortality, heart failure hospitalization, ventricular arrhythmia, stroke or myocardial infarction. PTT was measured automatically from low-resolution AIF dynamic series of both the LV and RV during rest perfusion imaging, and the PTT was measured as the time (in seconds) between the centroid of the left (LV) and right ventricle (RV) indicator dilution curves.ResultsPatients (N = 294) were followed-up for median 2.0 years during which 37 patients (12.6%) had at least one MACE event. On univariate Cox regression analysis there was a significant association between PTT and MACE (Hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.08–1.25, P = 0.0001). There was also significant association between PTT and heart failure hospitalisation (HR 1.15, 95% CI 1.02–1.29, P = 0.02) and moderate correlation between PTT and N-terminal pro B-type natriuretic peptide (NT-proBNP, r = 0.51, P < 0.001). PTT remained predictive of MACE after adjustment for clinical and imaging factors but was no longer significant once adjusted for NT-proBNP.ConclusionsPTT measured automatically during CMR perfusion imaging in patients with recent onset non-ischaemic heart failure is predictive of MACE and in particular heart failure hospitalisation. PTT derived in this way may be a non-invasive marker of haemodynamic congestion in heart failure and future studies are required to establish if prolonged PTT identifies those who may warrant closer follow-up or medicine optimisation to reduce the risk of future adverse events.

Pial collaterals limit stroke progression and metabolic stress in hypoperfused tissue: An MRI perfusion and mq-BOLD study.

In acute ischemic stroke (AIS) due to large-vessel occlusion (LVO), the relationship between cerebral oxygen extraction fraction (OEF) as the hallmark of the ischemic penumbra and leptomeningeal collateral supply is not well established. We aimed to investigate the relationship between pial collateralization and tissue oxygen extraction in patients with LVO using magnetic resonance imaging (MRI). Data from 14 patients with anterior circulation LVO who underwent MRI before acute stroke treatment were analyzed. In addition to diffusion-weighted imaging and perfusion-weighted imaging (PWI), the protocol comprised sequences for multiparametric quantitative blood-oxygen-level-dependent imaging for the calculation of relative OEF (rOEF). Pial collateral supply was quantitatively assessed by analyzing the signal variance in T2*-weighted PWI time series. Relationships between collateral supply, infarct volume, rOEF in peri-infarct hypoperfused tissue, and clinical stroke severity were assessed. The PWI-based parameter quantifying collateral supply was negatively correlated with baseline ischemic core volume and rOEF in the hypoperfused peri-infarct area (p<.01). Both reduced collateral supply and increased rOEF correlated significantly with higher scores on the National Institutes of Health Stroke Scale (p<.05). Increased rOEF within hypoperfused tissue was associated with higher baseline (p=.043) and follow-up infarct volume (p=.009). Signal variance-based mapping of collaterals with PWI depicts pial collateral supply, which is closely tied to tissue pathophysiology and clinical and imaging outcomes. Magnetic-resonance-derived mapping of cerebral rOEF reveals penumbral characteristics of hypoperfused tissue and might provide a promising imaging biomarker in AIS.

Comparison of myocardial perfusion study and invasive hemodynamic measurement of the significance of non-infarct-related residual stenoses in ST elevation myocardial infarction patients.

Nearly 50% of ST elevation myocardial infarction (STEMI) patients have multivessel coronary artery disease. The optimal selection of non-culprit lesions for complete revascularization is a matter of current debate. Little is known about the predictive value of myocardial perfusion study (MPS) in this scenario. We enrolled 49 STEMI patients (61.5 ± 10.3 years) with at least one major non-culprit lesion (50-90%) other than left main coronary artery lesions. Overall 63 non-infarct- related artery (IRA) stenoses (65.2 ± 11.9%) were recommended for further evaluation using Fractional Flow Reserve (FFR) measurement as is standard in our institution. Prior to FFR, all patients were scheduled for non-invasive MPS using single-photon emission computed tomography (SPECT). Both FFR and MPS were performed 4-8 weeks after STEMI with MPS preceding FFR within no more than 48 hours. An FFR value of ≤0.80 was considered significant and guided the final revascularization strategy. The results of MPS were correlated to FFR as well as to the clinical and angiographic characteristics of both culprit and non-infarct-related lesions. Based on FFR, 30 out of 63 stenoses (47.6%) in 27 patients were considered hemodynamically significant (FFR 0.69 ± 0.08, range 0.51-0.79) compared to residual 33 stenoses considered negative (FFR 0.87 ± 0.04, range 0.81-0.96). The MPS revealed abnormal myocardium (23.6% average, range 5-56%) in 21 patients (42.8%). Among those patients, only 9 showed the evidence of ischemic myocardium (average 10.8%, range 4-18%) with low sensitivity of MPS in predicting positive FFR. Besides that, higher proportion of patients (71.4% vs. 42.9%, P=0.047) with overall lower FFR values (0.73 vs. 0.80, P=0.014, resp.) in non-IRAs as well as higher proportion of patients with more severely compromised flow in IRAs (P=0.048) during STEMI had MPS-detected abnormal myocardium. In STEMI patients with multivessel coronary artery disease, we observed rather weak correlation between MPS using SPECT and invasive hemodynamic measurement using FFR in ischemia detection.

IMG-22. ASL PERFUSION LIGHTBULB SIGN: A POTENTIAL PATHOGNOMONIC FEATURE OF PEDIATRIC POSTERIOR FOSSA HEMANGIOBLASTOMA

Abstract INTRODUCTION Hemangioblastoma is a rare vascular tumor which occurs within the central nervous system in children. Differentiating hemangioblastoma from other posterior fossa tumors can be challenging on imaging and preoperative diagnosis can change neurosurgical approach. We hypothesize a ‘lightbulb sign’ (diffuse homogenous intense hyperperfusion within solid component of tumor) will help differentiate hemangioblastoma from other posterior fossa tumors. METHODS In this retrospective case-control study, we only included pathology-proven cases of hemangioblastoma, while the control group consisted of other randomly selected pathology-proven posterior fossa tumors from January 2022 to January 2024. Two blinded neuroradiologists analyzed all applicable MRI sequences. Their perfusion analysis also included the “lightbulb sign” as an extra criterion. Disagreements between the radiologists were confirmed by a third pediatric neuroradiologist. Chi-square and Fisher’s exact test were used to analyze the data. RESULTS 95 patients were enrolled in the study, 57(60%) were male. The median age at diagnosis was 8 (IQR: 3-14). Out of the enrolled patients, 8 had hemangioblastoma, and 87 had other posterior fossa tumors, including medulloblastoma (n=31), pilocytic astrocytoma (n=23), posterior fossa ependymoma type A (n=16), and other tumors (n=17). The comparison of hemangioblastoma vs non-hemangioblastoma showed that peripheral edema (p=0.020, OR=1.8) and T2 flow void (p=0.021, OR=1.7) favors hemangioblastoma, whereas reduced diffusion (low ADC) (p=0.002, OR=2.3) and ventricular system extension (p=0.001, OR=2.4) favors non-hemangioblastoma tumors. 42 cases also had perfusion studies. While high perfusion favors hemangioblastoma (p=0.021, OR=2.9), the lightbulb sign shows a complete distinction since all the ASL series of hemangioblastoma cases (n=4) showed the lightbulb sign, whereas none of the non-hemangioblastoma cases (n=38) showed the sign (p&amp;lt;0.001). CONCLUSION Lightbulb-like intense and homogenous hyperperfusion pattern on ASL allows differentiation of hemangioblastoma from other posterior fossa tumors in children.

Role of Clinical and Multimodality Neuroimaging in the Evaluation of Brain Death/Death by Neurologic Criteria and Recent Highlights from 2023 Updated Guidelines.

Purpose of Review: This review aims to provide a comprehensive overview of the diagnosis of brain death/death by neurologic criteria (BD/DNC) by emphasizing the clinical criteria established by the American Academy of Neurology (AAN) in light of their updated guidelines released in 2023. In this review, we will focus on the current implementation of ancillary tests including the catheter cerebral angiogram, nuclear scintigraphy, and transcranial Doppler, which provide support in diagnoses when clinical examination and apnea tests are inconclusive. Finally, we will also provide examples to discuss the implementation of certain imaging studies in the context of diagnosing BD/DNC. Recent Findings: Recent developments in the field of neurology have emphasized the importance of clinical criteria for diagnosing BD/DNC, with the AAN providing clear updated guidelines that include coma, apnea, and the absence of brainstem reflexes. Current ancillary tests, including the catheter cerebral angiogram, nuclear scintigraphy, and transcranial Doppler play a crucial role in confirming BD/DNC when the clinical assessment is limited. The role of commonly used imaging studies including computed tomography and magnetic resonance angiographies of the brain as well as CT/MR perfusion studies will also be discussed in the context of these new guidelines. Summary: BD/DNC represents the permanent cessation of brain functions, including the brainstem. This review article provides the historical context, clinical criteria, and pathophysiology that goes into making this diagnosis. Additionally, it explores the various ancillary tests and selected imaging studies that are currently used to diagnose BD/DNC under the newly updated AAN guidelines. Understanding the evolution of how to effectively use these diagnostic tools is crucial for healthcare professionals who encounter these BD/DNC cases in their practice.

Ex Vivo Vascular Imaging and Perfusion Studies of Normal Kidney and Tumor Vasculature.

This work describes a comprehensive study of the vascular tree and perfusion characteristics of normal kidney and renal cell carcinoma. Methods: Nephrectomy specimens were perfused ex-vivo, and the regional blood flow was determined by infusion of radioactive microspheres. The vascular architecture was characterized by micronized barium sulphate infusion. Kidneys were subsequently sagitally sectioned, and autoradiograms were obtained to show the perfusate flow in relation to adjacent contact X-ray angiograms. Vascular resistance in defined tissue compartments was quantified, and finally, the tumor vasculature was 3D reconstructed via the micro-CT technique. Results show that the vascular tree of the kidney could be distinctly defined, and autoradiograms disclosed a high cortical flow. The peripheral resistance unit of the whole perfused specimen was 0.78 ± 0.40 (n = 26), while that of the renal cortex was 0.17 ± 0.07 (n = 15 with 114 samples). Micro-CT images from both cortex and medulla defined the vascular architecture. Angiograms from the renal tumors demonstrated a significant vascular heterogeneity within and between different tumors. A dense and irregular capillary network characterized peripheral tumor areas, whereas central parts of the tumors were less vascularized. Despite the dense capillarity, low perfusion through vessels with a diameter below 15 µm was seen on the autoradiograms. We conclude that micronized barium sulphate infusion may be used to demonstrate the vascular architecture in a complex organ. The vascular resistance was low, with little variation in the cortex of the normal kidney. Tumor tissue showed a considerable vascular structural heterogeneity with low perfusion through the peripheral nutritive capillaries and very poor perfusion of the central tumor, indicating intratumoral pressure exceeding the perfusion pressure. The merits and shortcomings of the various techniques used are discussed.

Development of a RP-HPLC method for simultaneous determination of atenolol, metoprolol tartrate and phenol red for in-situ rat intestinal perfusion studies

Single-pass intestinal perfusion (SPIP) method is a widely used experimental model to determine the intestinal permeability of drugs. These studies are performed in the presence of a reference standard (metoprolol, MT) and a zero permeability marker (phenol red, PR). Therefore, it is important to develop a validated method for simultaneous determination of the investigated compound along with MT and PR. The aim of this study was to develop a reversed phase high-performance liquid chromatography (RP-HPLC) method with UV-detection for the simultaneous determination of atenolol (ATN), MT, and PR in the perfusion medium used in SPIP experiments. Separation of compounds were performed using an InertSustain C18 (250 × 4.6 mm, 5 µm) HPLC column at 35 °C. The mobile phase was a mixture of acetonitrile and phosphate buffer (pH 7.0, 12.5 mM) in gradient elution, and was delivered at a flow rate of 1 mL/min. The acetonitrile ratio of the mobile phase increased linearly from 10 to 35 % over 15 min. The injection volume was 20 µL, and ATN, MT and PR were detected at 224 nm. The retention times under optimum HPLC conditions were 5.028 min, 12.401 min, and 13.507 min for ATN, MT and PR, respectively. The developed RP-HPLC method was validated for selectivity, specificity, calibration curve and range, accuracy and precision, carry-over effect, stability, reinjection reproducibility, recovery and robustness. The method was linear for ATN (0.76–50 μg/mL), MT (1.14–50 μg/mL), and PR (0.47–20 μg/mL) with determination coefficients of 0.9999, 0.9994 and 0.9998, respectively. The results obtained for all validation parameters of the developed RP-HPLC method met the required limits of the ICH M10 Guideline.