Changes In Regional Perfusion Research Articles

Abstract 55: Mouse Offspring Exposed to Preeclampsia/Eclampsia-like Symptoms Exhibit Changes in Regional Cerebral Perfusion at 2 months of age

Children born to mothers with preeclampsia, a hypertensive pregnancy disorder, or eclampsia, new-onset seizures during pregnancy, are more likely to develop learning and memory deficits and are more susceptible to neurovascular diseases compared to those born from normal pregnancies. The contributing mechanisms are unknown. The objective of this study was to determine whether mice exposed to reduced uteroplacental perfusion (RUPP), to mimic preeclampsia with or without pentylenetetrazol (PTZ) injection (to induce seizures and model eclampsia), results in regional cerebral perfusion changes at 2 months of age. On gestational day (GD) 13.5, pregnant C57BL/6 mice underwent sham or RUPP surgery followed by injection or no treatment with PTZ (40 mg/kg) on GD 18.5. At 2 months of age, cerebral perfusion was measured using Laser Speckle Imaging, and averaged to obtain mean data per sex, per litter (n = 3-6 average datapoints per group). Perfusion data were normalized to the area of each region of interest. Data were analyzed using Two-Way ANOVA. Our findings indicate a reduction in cerebral perfusion in offspring exposed indirectly to RUPP specifically of the right parietal cortex (p = 0.013), superior sagittal sinus (p = 0.003), cerebellum (p = 0.003) and whole brain (p = 0.021). We also observed an overall significant reduction in perfusion, after indirect PTZ exposure, in the right parietal cortex (p = 0.002), transverse sinus (p = 0.003), and cerebellum (p < 0.001); and increase in prefrontal cortex perfusion (p = 0.001). Further observation showed an overall difference in hematocrit (p = 0.001), SPO2 (p < 0.001), and cerebellum water content (p = 0.007) after indirect PTZ exposure. There was no difference in perfusion of the left parietal cortex, body weight, organ weight (except brain, where RUPP exposure led to overall increased brain weight; p = 0.030). Together, our results are consistent with the hypothesis that exposure to preeclampsia/eclampsia conditions leads to changes in offspring cerebrovascular function, with a net reduction in perfusion. Reduced cerebral perfusion is generally associated with reduced cognitive function. Whether this occurs along with changes in capillary density, or is exacerbated with age are areas of active investigation.

Brain perfusion changes in beta-thalassemia

BackgroundBrain injury in hereditary hemoglobinopathies is commonly attributed to anemia-related relative hypoperfusion in terms of impaired oxygen blood supply. Supratentorial and infratentorial vascular watershed regions seem to be especially vulnerable, but data are very scarce.AimsWe investigated a large beta-thalassemia sample with arterial spin labeling in order to characterize regional perfusion changes and their correlation with phenotype and anemia severity.MethodsWe performed a multicenter single-scanner cross-sectional 3T-MRI study analyzing non-invasively the brain perfusion in 54 transfusion-dependent thalassemia (TDT), 23 non-transfusion-dependent thalassemia (NTDT) patients and 56 Healthy Controls (HC). Age, hemoglobin levels, and cognitive functioning were recorded.ResultsBoth TDT and NTDT patients showed globally increased brain perfusion values compared to healthy controls, while no difference was found between patient subgroups. Using age and sex as covariates and scaling the perfusion maps for the global cerebral blood flow, beta-thalassemia patients showed relative hyperperfusion in supratentorial/infratentorial watershed regions. Perfusion changes correlated with hemoglobin levels (p = 0.013) and were not observed in the less severely anemic patients (hemoglobin level > 9.5 g/dL). In the hyperperfused regions, white matter density was significantly decreased (p = 0.0003) in both patient subgroups vs. HC. In NTDT, white matter density changes correlated inversely with full-scale Intelligence Quotient (p = 0.007) while in TDT no correlation was found.ConclusionRelative hyperperfusion of watershed territories represents a hemodynamic hallmark of beta-thalassemia anemia challenging previous hypotheses of brain injury in hereditary anemias. A careful management of anemia severity might be crucial for preventing structural white matter changes and subsequent long-term cognitive impairment.

Longitudinal Brain Perfusion and Symptom Presentation Following Pediatric Concussion: A Pediatric Concussion Assessment of Rest and Exertion+MRI (PedCARE+MRI) Substudy.

Emerging evidence suggests that advanced neuroimaging modalities such as arterial spin labelling (ASL) might have prognostic utility for pediatric concussion. This study aimed to: 1) examine group differences in global and regional brain perfusion in youth with concussion or orthopedic injury (OI) at 72 h and 4 weeks post-injury; 2) examine patterns of abnormal brain perfusion within both groups and their recovery; 3) investigate the association between perfusion and symptom burden within concussed and OI youths at both time-points; and 4) explore perfusion between symptomatic and asymptomatic concussed and OI youths. Youths ages 10.00-17.99 years presenting to the emergency department with an acute concussion or OI were enrolled. ASL-magnetic resonance imaging scans were conducted at 72 h and 4 weeks post-injury to measure brain perfusion, along with completion of the Health Behavior Inventory (HBI) to measure symptoms. Abnormal perfusion clusters were identified using voxel-based z-score analysis at each visit. First, mixed analyses of covariance (ANCOVAs) investigated the Group*Time interaction on global and regional perfusion. Post hoc region of interest (ROI) analyses were performed on significant regions. Second, within-group generalized estimating equations investigated the recovery of abnormal perfusion at an individual level. Third, multiple regressions at each time-point examined the association between HBI and regional perfusion, and between HBI and abnormal perfusion volumes within the concussion group. Fourth, whole-brain one-way ANCOVAs explored differences in regional and abnormal perfusion based on symptomatic status (symptomatic vs. asymptomatic) and OIs at each time-point. A total of 70 youths with a concussion [median age (interquartile range; IQR) = 12.70 (11.67-14.35), 47.1% female] and 29 with an OI [median age (IQR) = 12.05 (11.18-13.89), 41.4% female] were included. Although no Group effect was found in global perfusion, the concussion group showed greater adjusted perfusion within the anterior cingulate cortex/middle frontal gyrus (MFG) and right MFG compared with the OI group across time-points (ps ≤ 0.004). The concussion group showed lower perfusion within the right superior temporal gyrus at both time-points and bilateral occipital gyrus at 4 weeks, (ps ≤ 0.006). The number of hypoperfused clusters was increased at 72 h compared with 4 weeks in the concussion youths (p < 0.001), but not in the OIs. Moreover, Group moderated the HBI-perfusion association within the left precuneus and superior frontal gyrus at both time-points, (ps ≤ 0.001). No association was found between HBI and abnormal perfusion volume within the concussion group at any visits. At 4 weeks, the symptomatic sub-group (n = 10) showed lower adjusted perfusion within the right cerebellum and lingual gyrus, while the asymptomatic sub-group (n = 59) showed lower adjusted perfusion within the left calcarine, but greater perfusion within the left medial orbitofrontal cortex, right middle frontal gyrus, and bilateral caudate compared with OIs. Yet, no group differences were observed in the number of abnormal perfusion clusters or volumes at any visit. The present study suggests that symptoms may be associated with changes in regional perfusion, but not abnormal perfusion levels.

Ultrasound and magnetic resonance imaging–based investigation of the role of perfusion and oxygen availability in menstrual pain

BackgroundThe mechanisms responsible for menstrual pain are poorly understood. However, dynamic noninvasive pelvic imaging of menstrual pain sufferers could aid in identifying therapeutic targets and in testing novel treatments. ObjectiveTo study the mechanisms responsible for menstrual pain, we analyzed ultrasonographic and complementary functional Magnetic Resonance Imaging (fMRI) parameters in dysmenorrhea sufferers and pain-free controls under multiple conditions. Study DesignWe performed fMRI on participants with and without dysmenorrhea during menses and non-menses. To clarify whether regional changes in oxygen availability and perfusion occur, fMRI R2* measurements were made of the endometrium and myometrium. R2* measurements are calculated nuclear magnetic resonance relaxation rates sensitive to the paramagnetic properties of oxygenated and deoxygenated hemoglobin. We also compared parameters before and after an analgesic dose of naproxen sodium. In addition, we performed similar measurements with Doppler ultrasonography to identify whether changes in uterine arterial velocity occurred during menstrual cramping in real time. Mixed model statistics were performed to account for within-subject effects across conditions. Corrections for multiple comparisons were made with a false discovery rate adjustment. ResultsDuring menstruation, a notable increase in R2* values, indicative of tissue ischemia, was observed in both the myometrium (beta ± standard error of the mean: 15.74 ± 2.29 s-1, p = 0.001, q = 0.002) and the endometrium (26.37 ± 9.33 s-1, p = 0.005, q = 0.008) among participants experiencing dysmenorrhea. A similar increase was noted in the myometrium (28.89 ± 2.85 s-1, p = 0.001, q = 0.002) and endometrium (75.50 ± 2.57 s-1, p = 0.001, q = 0.003) among pain-free controls. Post-hoc analyses revealed that R2* values during menstruation were significantly higher than those in participants with dysmenorrhea (Myometrium: p = 0.008, Endometrium: p = 0.043). Whereas naproxen sodium increased endometrial R2* in participants with dysmenorrhea (48.29 ± 15.78 s-1,p = 0.005, q = 0.008), it decreased myometrial R2*in pain-free controls. Doppler findings were consistent with fMRI (-8.62 ± 3.25 s-1, p = 0.008, q = 0.011). The pulsatility index (-0.42 ± 0.14, p = 0.004, q = 0.004) and resistance index (-0.042 ± 0.012, p = 0.001, q = 0.001) decreased during menses compared with non-menses, and effects were significantly reversed by naproxen sodium. Naproxen sodium had the opposite effect in pain-free controls. There were no significant real-time changes in the pulsatility index, resistance index, peak systolic velocity, or minimum diastolic velocity during episodes of symptomatic menstrual cramping. ConclusionsfMRI and Doppler metrics suggest participants with dysmenorrhea have better perfusion and oxygen availability than pain-free controls. Naproxen sodium's therapeutic mechanism is associated with relative reductions in uterine perfusion and oxygen availability. An opposite pharmacological effect was observed in pain-free controls. During menstrual cramping, there is insufficient evidence of episodic impaired uterine perfusion. Thus, prostaglandins may have protective vasoconstrictive effects in pain-free controls and opposite effects among participants with dysmenorrhea.

Abnormalities in Regional Cerebral Blood Flow Due to Headache in a COVID-19 Infected Patient Observed on 99mTC-ECD Brain SPECT/CT

A 31-year-old man was diagnosed with a COVID-19 infection, presenting with a diffuse headache and an uneven sensation of fullness, despite having no prior systemic diseases. 99mTc-ECD Brain SPECT/CT revealed a marked decrease in blood perfusion in the cerebral cortices, predominantly in the frontal region and involving the olfactory sulcus. In contrast, there was increased perfusion in the occipital lobe and asymmetrical perfusion in the cerebellum. This case highlights changes in regional blood flow perfusion that might affect the functional connectivity of the pain matrix, leading to the onset of headaches and associated underlying mechanisms.

Effects of β‐amyloid deposition, dopaminergic depletion, and perfusion on clinical features in cognitively impaired patients

AbstractBackgroundAlthough mixed pathologies are common in Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB), effects of β‐amyloid and dopaminergic depletion on brain perfusion and clinical features have not been elucidated.MethodIn 99 patients with cognitive impairment due to AD and/or DLB and 32 control participants, 18F‐Florbetaben (FBB) PET, dual‐phase dopamine transporter (DAT) PET, and brain MRI were performed to measure β‐amyloid standardized uptake value ratio (SUVR), dopaminergic depletion in the ventral striatum, caudate, and putamen, and regional brain perfusion. Cognitive score, visual hallucination (VH), cognitive fluctuation (CF), and rapid eye movement sleep behavior disorder (RBD) were evaluated. Relationship among global FBB‐SUVR, striatal DAT uptakes, regional brain perfusion, clinical symptoms, and cognitive scores were evaluated using general linear or logistic regression models as appropriate.ResultGlobal and mean lobar FBB SUVRs negatively correlated with DAT uptakes in the ventral striatum and caudate but not with putamen DAT uptake. Lower ventral striatal DAT uptake was associated with right temporo‐parietal hypoperfusion and hyper‐perfusion in the anterior cingulate cortex, vermis, motor cortex, and hippocampus, while higher FBB SUVR was associated with hypoperfusion in the left entorhinal cortex and temporo‐parietal cortex. Lower ventral striatal DAT uptake increased the risks of VH and RBD directly and indirectly through the mediation of hippocampal hyper‐perfusion, while hippocampal hyper‐perfusion fully mediated the effect of lower ventral striatal DAT uptake on the risk of CF. Higher FBB SUVR and lower DAT uptake were associated with language, memory, and executive dysfunction directly and indirectly through the mediation of regional perfusion, while regional perfusion fully mediated their effects on visuospatial dysfunction.Conclusionβ‐amyloid deposition and striatal dopaminergic depletion reflecting AD‐ and DLB‐related neurodegenerations are inter‐correlated but differently contribute to regional perfusion changes and cognitive dysfunction.

Assessing the Role of PLCG2*M28L Risk In A Novel Mouse Model Late‐Onset Alzheimer’s Disease

AbstractBackgroundMODEL‐AD has developed and characterized novel mouse models that aim to better phenocopy human LOAD for preclinical testing. More than 40 different models carrying combinations of LOAD risk factors have been created and assessed for relevance to LOAD. In this study, we aim to determine the mechanisms by which variations in the phospholipase C gamma 2 (PLCG2) gene increase risk for LOAD.MethodsThe M28L variant in PLCG2 (PLCG2*M28L) was prioritized as a LOAD risk factor. Mice were generated by CRISPR/CAS9 introduction of Plcg2*M28L variant on to LOAD1 (B6.APOE4.Trem2*R47H) and transcriptional profiling of brain hemispheres from 12 months old mice was used to evaluate molecular effects of Plcg2*M28L. To evaluate the contribution of Plcg2*M28L to LOAD risk, mice where placed on control or high fat diet (HFD) to serve as an environmental driver of neuroinflammation. Female and male LOAD1.Plcg2*M28L and LOAD1 control mice are being characterized at 4 and 12 mos through the MODEL‐AD phenotyping pipeline, which includes in vivo imaging of brain perfusion and glycolytic metabolism, multi‐omics, fluid biomarkers, cognition, and neuropathology.ResultsLOAD1.Plcg2*M28L mice showed brain transcriptomic alignment at 12 mos to human LOAD, and was prioritized for deep phenotyping. LOAD1 mice on HFD showed significant regional reductions in brain glycolysis and increased perfusion relative to controls yielding an uncoupled phenotype. By contrast, LOAD1.Plcg2*M28L mice showed a little to no regional changes in brain glycolysis or perfusion and few uncoupled regions. Multi‐resolution connectomics revealed a decrease in cluster number and organization in LOAD1 but not LOAD1.Plcg2*M28L for both sexes fed HFD compared with control diets. By 12 mos, male and female LOAD1.Plcg2*M28L mice on HFD showed opposite changes in clustering coefficient, network degree, and network density, with males showing a decrease and females an increase relative to controls. Mice carrying Plcg2*M28L variants are also being phenotyping at 18 and 24 mos.ConclusionsData collected to date reveal Plcg2*M28L on a LOAD1 background showed fewer sex‐dependent change in metabolism, perfusion and uncoupling on HFD when compared to LOAD1. These data suggest that the Plcg2*M28L risk variant on the LOAD1 background may result in an attenuated TREM2 signaling.

Changes in postictal cerebral perfusion are related to the duration of electroconvulsive therapy-induced seizures.

Postictal symptoms may result from cerebral hypoperfusion, which is possibly a consequence of seizure-induced vasoconstriction. Longer seizures have previously been shown to cause more severe postictal hypoperfusion in rats and epilepsy patients. We studied cerebral perfusion after generalized seizures elicited by electroconvulsive therapy (ECT) and its relation to seizure duration. Patients with a major depressive episode who underwent ECT were included. During treatment, 21-channel continuous electroencephalogram (EEG) was recorded. Arterial spin labeling magnetic resonance imaging scans were acquired before the ECT course (baseline) and approximately 1 h after an ECT-induced seizure (postictal) to quantify global and regional gray matter cerebral blood flow (CBF). Seizure duration was assessed from the period of epileptiform discharges on the EEG. Healthy controls were scanned twice to assess test-retest variability. We performed hypothesis-driven Bayesian analyses to study the relation between global and regional perfusion changes and seizure duration. Twenty-four patients and 27 healthy controls were included. Changes in postictal global and regional CBF were correlated with seizure duration. In patients with longer seizure durations, global decrease in CBF reached values up to 28 mL/100 g/min. Regional reductions in CBF were most prominent in the inferior frontal gyrus, cingulate gyrus, and insula (up to 35 mL/100 g/min). In patients with shorter seizures, global and regional perfusion increased (up to 20 mL/100 g/min). These perfusion changes were larger than changes observed in healthy controls, with a maximum median global CBF increase of 12 mL/100 g/min and a maximum median global CBF decrease of 20 mL/100 g/min. Seizure duration is a key factor determining postictal perfusion changes. In future studies, seizure duration needs to be considered as a confounding factor due to its opposite effect on postictal perfusion.

Effects of amyloid beta and dopaminergic depletion on perfusion and clinical symptoms.

Although mixed pathologies are common in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), the effects of amyloid beta and dopaminergic depletion on brain perfusion and clinical symptoms have not been elucidated. In 99 cognitive impairment patients due to AD and/or DLB and 32 controls, 18F-florbetaben (FBB) and dual-phase dopamine transporter (DAT) positron emission tomography (PET) were performed to measure the FBB standardized uptake value ratio (SUVR), striatal DAT uptakes, and brain perfusion. Higher FBB-SUVR and lower ventral striatal DAT uptake were intercorrelated and, respectively, associated with left entorhinal/temporo-parietal-centered hypoperfusion and vermis/hippocampal-centered hyperperfusion, whereas regional perfusion mediated clinical symptoms and cognition. Amyloid beta deposition and striatal dopaminergic depletion contribute to regional perfusion changes, clinical symptoms, and cognition in the spectrum of normal aging and cognitive impairment due to AD and/or LBD. Amyloid beta (Aβ) deposition was associated with ventral striatal dopaminergic depletion. Aβ deposition and dopaminergic depletion correlated with perfusion. Aβ deposition correlated with hypoperfusion centered in the left entorhinal cortex. Dopaminergic depletion correlated with hyperperfusion centered in the vermis. Perfusion mediated the Aβ deposition/dopaminergic depletion's effects on cognition.

Changes in myocardial perfusion according to left ventricular pacing site in cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): 1. The Danish Heart Foundation 2. The Health Research Fund of the Central Denmark Region Background/Introduction Changes in left ventricular (LV) myocardial perfusion according to LV pacing site during cardiac resynchronization therapy (CRT) has only been sparsely described. Purpose To assess changes in LV global and regional myocardial perfusion according to LV pacing site after six months CRT. Methods Data from patients enrolled in the randomized controlled trial "Electrically vs. Imaging-guided Left Ventricular Lead Placement in Cardiac Resynchronization Therapy" was evaluated. Global and segmental absolute myocardial perfusion in ml/g/min was assessed by 82Rb-PET the day before CRT implantation and at six-months follow-up (6MFU). The exact LV pacing site was determined by post-implant cardiac CT. Perfusion and pacing site were evaluated using the standard 17’-segment LV model. Echocardiographic assessment of LV ejection fraction (EF) was performed the day before CRT implantation and at 6MFU. Results 93 patients (age 71±9 years; ischemic heart disease 48%; female 25%; median QRS 166±20 ms; mean LVEF 30±7%; NYHA class I/II/III/IV (%) 0/63/33/3) were included. Distribution of LV pacing sites is shown in Figure 1. No change in LV global perfusion was observed from baseline to 6MFU (0.79 to 0.81 ml/g/min, P=0.41; respectively). LV EF increased by 9±10%. Baseline global perfusion was higher in the 39 patients in whom LV EF had increased ≥10% at 6MFU (0.86 vs. 0.74 ml/g/min, P=0.02; respectively). However, no difference in perfusion-change was observed between patients with ≥10% increase in LV EF at 6MFU and patients with &amp;lt;10% increase (0.01 vs. 0.02 ml/g/min, P=0.76; respectively). Baseline perfusion was higher in the segments chosen for LV-pacing than in the non-paced segments (0.96 vs. 0.78 ml/g/min, P=0.00; respectively). Perfusion in the paced segments dropped to 0.86 ml/g/min (P=0.00) at 6MFU. Perfusion in the neighbouring segments also dropped during six months (from 0.91 to 0.86 ml/g/min, P=0.03), while perfusion in the non-paced and non-neighbouring segments increased (from 0.75 to 0.80 ml/g/min, P=0.01). Conclusion Despite a mean increase in LV EF of 9%, global myocardial perfusion remained unchanged. CRT resulted in a homogenous distribution of myocardial perfusion with a decreased perfusion in segments concordant and adjacent to LV pacing site and a corresponding increased perfusion in remote segments.

Modulation of pulmonary blood flow in patients with acute respiratory failure

BackgroundImpairment of ventilation and perfusion (V/Q) matching is a common mechanism leading to hypoxemia in patients with acute respiratory failure requiring intensive care unit (ICU) admission. While ventilation has been thoroughly investigated, little progress has been made to monitor pulmonary perfusion at the bedside and treat impaired blood distribution. The study aimed to assess real-time changes in regional pulmonary perfusion in response to a therapeutic intervention. MethodsSingle-center prospective study that enrolled adult patients with ARDS caused by SARS-Cov-2 who were sedated, paralyzed, and mechanically ventilated. The distribution of pulmonary perfusion was assessed through electrical impedance tomography (EIT) after the injection of a 10-ml bolus of hypertonic saline. The therapeutic intervention consisted in the administration of inhaled nitric oxide (iNO), as rescue therapy for refractory hypoxemia. Each patient underwent two 15-min steps at 0 and 20 ppm iNO, respectively. At each step, respiratory, gas exchange, and hemodynamic parameters were recorded, and V/Q distribution was measured, with unchanged ventilatory settings. ResultsTen 65 [56–75] years old patients with moderate (40%) and severe (60%) ARDS were studied 10 [4-20] days after intubation. Gas exchange improved at 20 ppm iNO (PaO2/FiO2 from 86 ± 16 to 110 ± 30 mmHg, p = 0.001; venous admixture from 51 ± 8 to 45 ± 7%, p = 0.0045; dead space from 29 ± 8 to 25 ± 6%, p = 0.008). The respiratory system's elastic properties and ventilation distribution were unaltered by iNO. Hemodynamics did not change after gas initiation (cardiac output 7.6 ± 1.9 vs. 7.7 ± 1.9 L/min, p = 0.66). The EIT pixel perfusion maps showed a variety of patterns of changes in pulmonary blood flow, whose increase positively correlated with PaO2/FiO2 increase (R2 = 0.50, p = 0.049). ConclusionsThe assessment of lung perfusion is feasible at the bedside and blood distribution can be modulated with effects that are visualized in vivo. These findings might lay the foundations for testing new therapies aimed at optimizing the regional perfusion in the lungs.

Cardiac output affects the response to pulsed inhaled nitric oxide in mechanically ventilated anesthetized ponies determined by CT angiography of the lung.

To measure changes in regional lung perfusion using CT angiography in mechanically ventilated, anesthetized ponies administered pulsed inhaled nitric oxide (PiNO) during hypotension and normotension. 6 ponies for anesthetic 1 and 5 ponies for anesthetic 2. Ponies were anesthetized on 2 separate occasions, mechanically ventilated, and placed in dorsal recumbency within the CT gantry. Pulmonary arterial, right atrial, and facial arterial catheters were placed. During both anesthetics, PiNO was delivered for 60 minutes and then discontinued. Anesthetic 1: hypotension (mean arterial pressure < 70 mmHg) was treated using dobutamine after 30 minutes of PiNO delivery. Following the discontinuation of PiNO, dobutamine administration was discontinued in 3 ponies and was continued in 3 ponies. The lung was imaged at 30, 60, and 105 minutes. Anesthetic 2: hypotension persisted throughout anesthesia. The lung was imaged at 30, 60, and 90 minutes. At all time points, arterial and mixed venous blood samples were analyzed and cardiac output (Q˙t) was measured. Pulmonary perfusion was calculated from CT image analysis. During PiNO delivery, perfusion to well-ventilated lungs increased if ponies were normotensive, leading to increased arterial oxygenation, reduced alveolar dead space, and reduced alveolar to arterial oxygen tension gradient. When PiNO was stopped and dobutamine administration continued, alveolar dead space and venous admixture increased, in contrast to when dobutamine and PiNO were both discontinued. If PiNO is administered to mechanically ventilated, anesthetized ponies with concurrent hypotension and low Q˙t, this must be supported to achieve favorable redistribution of pulmonary perfusion to improve pulmonary gas exchange.

The impact of a high-sodium diet regimen on cerebrovascular morphology and cerebral perfusion in Alzheimer's disease.

Various lifestyle factors such as chronic hypertension and a high-sodium diet regimen are shown to impact cerebrovascular morphology and structure. Unusual cerebrovascular morphological and structural changes may contribute to cerebral hypoperfusion in Alzheimer's disease (AD). The objective of this study was to examine whether a high-sodium diet mediates cerebrovascular morphology and cerebral perfusion alterations in AD. Double transgenic mice harboring Aβ precursor protein (APPswe) and presenilin-1 (PSEN1) along with wild-type controls were divided into four groups. Group A (APP/PS1) and B (controls) were both fed a high-sodium (4.00%), while group C (APP/PS1) and D (controls) were both fed alow-sodium (0.08% a regular chow diet) for three months. Then, changes in regional cerebral perfusion and diffusion, cerebrovascular morphology, and structure were quantified. A 3-month high-sodium diet causes pyknosis and deep staining in hippocampal neurons and reduced vascular density in both hippocampal and cortical areas (p <0.001) of APP/PS1. Despite vascular density changes, cerebral perfusion was not increased markedly (p=0.3) in this group, though it was increased more in wild-type controls (p=0.022). A high-sodium diet regimen causes cerebrovascular morphology alteration in APP/PS1 mouse model of AD.

Coronary conductance in the normal development of sheep during the perinatal period.

Birth is associated with substantial shifts in cardiovascular physiology. Little is known about coronary vascular adaptations during this period. We used fetal and neonatal lambs to measure coronary function at late gestation (92% of term) and shortly after birth (5-6 days postnatal age). In each animal we measured unanesthetized myocardial perfusion and oxygen delivery using a circumflex artery flow probe. We used inflatable occluders and adenosine to determine coronary conductance and flow reserve. In a subset of animals, we used myocardial contrast echocardiography (MCE, anesthetized) to assess its utility as a tool for studying changes in regional myocardial perfusion in normal development. Separate age-matched animals were instrumented with aortic and coronary sinus sampling catheters to determine myocardial oxygen extraction (unanesthetized). With an average of 17 days of developmental time separating our neonatal and fetal cohorts we found that heart-to-body weight ratio was significantly greater in neonates than fetuses. In resting animals, we found significant decreases in weight-normalized perfusion of, and oxygen delivery to, neonatal relative to fetal myocardium. Similar results were seen when measuring baseline MCE-derived perfusion. Pressure-flow relationship studies revealed lower baseline and maximal coronary conductance in neonates than fetuses, with similar coronary flow reserve between groups. There was greater oxygen extraction in neonates than fetuses. Combined analysis of oxygen extraction with coronary flow suggested greater oxygen consumption by the fetal than neonatal myocardium. We conclude that, during the immediate perinatal period, cardiac growth outpaces coronary microvascular growth resulting in lower capacity for microvascular perfusion in the early neonate.

Arterial Spin-Labeling Perfusion Metrics in Pediatric Posterior Fossa Tumor Surgery.

Pediatric posterior fossa tumors often present with hydrocephalus; postoperatively, up to 25% of patients develop cerebellar mutism syndrome. Arterial spin-labeling is a noninvasive means of quantifying CBF and bolus arrival time. The aim of this study was to investigate how changes in perfusion metrics in children with posterior fossa tumors are modulated by cerebellar mutism syndrome and hydrocephalus requiring pre-resection CSF diversion. Forty-four patients were prospectively scanned at 3 time points (preoperatively, postoperatively, and at 3-month follow-up) with single- and multi-inflow time arterial spin-labeling sequences. Regional analyses of CBF and bolus arrival time were conducted using coregistered anatomic parcellations. ANOVA and multivariable, linear mixed-effects modeling analysis approaches were used. The study was registered at clinicaltrials.gov (NCT03471026). CBF increased after tumor resection and at follow-up scanning (P = .045). Bolus arrival time decreased after tumor resection and at follow-up scanning (P = .018). Bolus arrival time was prolonged (P = .058) following the midline approach, compared with cerebellar hemispheric surgical approaches to posterior fossa tumors. Multivariable linear mixed-effects modeling showed that regional perfusion changes were more pronounced in the 6 children who presented with symptomatic obstructive hydrocephalus requiring pre-resection CSF diversion, with hydrocephalus lowering the baseline mean CBF by 20.5 (standard error, 6.27) mL/100g/min. Children diagnosed with cerebellar mutism syndrome (8/44, 18.2%) had significantly higher CBF at follow-up imaging than those who were not (P = .040), but no differences in pre- or postoperative perfusion parameters were seen. Multi-inflow time arterial spin-labeling shows promise as a noninvasive tool to evaluate cerebral perfusion in the setting of pediatric obstructive hydrocephalus and demonstrates increased CBF following resolution of cerebellar mutism syndrome.

Regional impairment of deep gray matter perfusion in neonates with congenital heart disease revealed by arterial spin labeling MRI.

The present study examined deep gray matter perfusion in neonates with congenital heart disease (CHD) with arterial spin labeling magnetic resonance imaging preoperatively. We found that neonates with cyanotic CHD showed lower right thalamus compared with controls and lower right basal ganglia perfusion compared with acyanotic CHD. When the CHD group was assessed as a whole, it showed slightly decreased left thalamus perfusion compared with controls. The results suggest that cardiac physiology plays a crucial part in changes in regional cerebral perfusion. Perfusion with arterial spin labeling may be a useful marker of high risk for impaired cerebral blood flow auto-regulation and cerebral hypoperfusion in neonates with CHD.

Comparison of Acute Followed by Maintenance ECT vs Clozapine on Psychopathology and Regional Cerebral Blood Flow in Treatment-Resistant Schizophrenia: A Randomized Controlled Trial.

In treatment-resistant schizophrenia (TRS), Clozapine is only approved treatment with undesirable side-effects, warranting better alternatives. Our hypothesis is acute followed by maintenance Electroconvulsive Therapy (M-ECT) will be comparable in efficacy and safety to Clozapine in TRS. In this open-label trial, 60 TRS patients were randomized equally to M-ECT (following an acute-course) or Clozapine. Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Schizophrenia Scale (CGI-SCH), Montreal Cognitive Assessment (MoCA), and Global assessment of functioning (GAF) were measured and compared within and between the groups at baseline, 6 weeks, 12 weeks, and 24 weeks. SPECT-CT brain was done at baseline and 24 weeks to compare the changes in regional cerebral perfusion between the groups and correlate with the changes in the outcome-measures. The PANSS-T scores changes from baseline over the observation-points were significant in both M-ECT and clozapine groups (P < .001), with comparatively better reduction with M-ECT (P < .001). Similar trends were observed in PANSS subscales, CGI-SCH and GAF in both groups, with significantly better improvement with M-ECT over the study-period. After 24 weeks, there was significantly better perfusion with M-ECT in bilateral prefrontal and temporal cortices (P < .05). With M-ECT, a positive correlation was found between changes in PANSS-P scores and left-lateral Temporal cortical perfusion (r = .465, P = .017). Acute followed by M-ECT was more effective than clozapine over 6 months in reducing the positive and negative symptoms, general psychopathology, illness-severity, and improving the global functionality in TRS [clinicaltrials.gov: NCT03807882].

Impact of Medical Treatment of Hemodynamically Significant Patent Ductus Arteriosus on Cerebral and Renal Tissue Oxygenation Measured by Near-Infrared Spectroscopy in Very Low-Birth-Weight Infants.

Background and objective: Hemodynamically significant patent ductus arteriosus (hsPDA) can cause ductal steal and contribute to poor outcomes in preterm infants. Near-infrared spectroscopy (NIRS) allows us to continuously evaluate regional tissue oxygenation (rSpO2) and perfusion changes in underlying organs. The aim of this study was to evaluate the effect of medical treatment for hsPDA on cerebral and renal rSpO2 in infants less than 32 weeks of gestational age, and older than 72 h of life. Materials and methods: Infants with a gestational age of <32 weeks with hsPDA were prospectively studied before and during medical treatment. Two-site (cerebral and renal) rSpO2 monitoring by NIRS was performed 1 h before treatment (T0) and 24 h (T1), 24–48 h (T2), 48–72 h (T3) after the infusion of the first drug dose. Results: A total of 21 infants were studied. The mean day of life at treatment initiation was 8.2 (SD, 2.75). The DA diameter, LA/Ao ratio, and resistive index in the anterior cerebral artery (RI ACA) were significantly lower after treatment (p < 0.05). There were no significant differences in cerebral rSpO2, cerebral fractional tissue oxygen extraction (FTOE), and SpO2 comparing different time points. A significantly higher renal SpO2 value was recorded at T2 as compared with T0 (75.0%, SD 4.9%, vs. 69.4%, SD 7.6%; p < 0.013), while for renal FTOE, a tendency to lower values at T2 was observed (0.18, SD 0.05, vs. 0.24, SD 0.09; p = 0.068). Conclusions: Late (later than 7 days postpartum) hsPDA medical treatment with paracetamol or ibuprofen completely closed the duct only in a small proportion of preterm infants, despite a statistically significant reduction in the DA diameter, LA/Ao ratio, and RI ACA. Continuous renal, not cerebral, NIRS measurements can help to anticipate the efficacy of medical treatment of hsPDA in preterm infants. Large-scale prospective studies are needed to ascertain that renal and cerebral NIRS can be used as a reliable tool for evaluating the effectiveness of medical treatment for hsPDA.

Effects of pulsed inhaled nitric oxide delivery on the distribution of pulmonary perfusion in spontaneously breathing and mechanically ventilated anesthetized ponies.

To measure changes in pulmonary perfusion during pulsed inhaled nitric oxide (PiNO) delivery in anesthetized, spontaneously breathing and mechanically ventilated ponies positioned in dorsal recumbency. 6 adult ponies. Ponies were anesthetized, positioned in dorsal recumbency in a CT gantry, and allowed to breathe spontaneously. Pulmonary artery, right atrial, and facial artery catheters were placed. Analysis time points were baseline, after 30 minutes of PiNO, and 30 minutes after discontinuation of PiNO. At each time point, iodinated contrast medium was injected, and CT angiography was used to measure pulmonary perfusion. Thermodilution was used to measure cardiac output, and arterial and mixed venous blood samples were collected simultaneously and analyzed. Analyses were repeated while ponies were mechanically ventilated. During PiNO delivery, perfusion to aerated lung regions increased, perfusion to atelectatic lung regions decreased, arterial partial pressure of oxygen increased, and venous admixture and the alveolar-arterial difference in partial pressure of oxygen decreased. Changes in regional perfusion during PiNO delivery were more pronounced when ponies were spontaneously breathing than when they were mechanically ventilated. In anesthetized, dorsally recumbent ponies, PiNO delivery resulted in redistribution of pulmonary perfusion from dependent, atelectatic lung regions to nondependent aerated lung regions, leading to improvements in oxygenation. PiNO may offer a treatment option for impaired oxygenation induced by recumbency.

Lung Perfusion Assessment by Bedside Electrical Impedance Tomography in Critically Ill Patients.

As a portable, radiation-free imaging modality, electrical impedance tomography (EIT) technology has shown promise in the bedside visual assessment of lung perfusion distribution in critically ill patients. The two main methods of EIT for assessing lung perfusion are the pulsatility and conductivity contrast (saline) bolus method. Increasing attention is being paid to the saline bolus EIT method in the evaluation of regional pulmonary perfusion in clinical practice. This study seeks to provide an overview of experimental and clinical studies with the aim of clarifying the progress made in the use of the saline bolus EIT method. Animal studies revealed that the saline bolus EIT method presented good consistency with single-photon emission CT (SPECT) in the evaluation of lung regional perfusion changes in various pathological conditions. Moreover, the saline bolus EIT method has been applied to assess the lung perfusion in a pulmonary embolism and the effect of positive end-expiratory pressure (PEEP) on regional ventilation/perfusion ratio (V/Q) and acute respiratory distress syndrome (ARDS) in several clinical studies. The implementation of saline boluses, data analyses, precision, and cutoff values varied among different studies, and a consensus must be reached regarding the clinical application of the saline bolus EIT method. Further study is required to validate the impact of the described saline bolus EIT method on decision-making, therapeutic management, and outcomes in critically ill patients.