Dissecting aortic aneurysm and contrast magnetic resonance angiography

The propose of the present work is to study the potential of the 3-D contrast MR-angiography (MRA) in diagnosis of aortic dissection. The studied group consisted of 45 patients who as expected might have aortic dissection. 15 patients was observed in dynamics after surgical treatment. Total number of me performed contrast-MRA was 72. MRA has been performed on 1.5T MR tomograph Magnetom Vision (Siemens) with the of ultrafast sequenses Fisp and turbo-flash. Aortic dissection was diagnosed in 18 patients. The method of ce-MRA enables to make a precise diagnose of acute and chronic aortic dissection. This method is used for a dynamic follow up of the patients after the performed surgery.     

Anatomical and functional changes in the upper airways of sleep apnea patients due to mandibular repositioning: a large scale study

The obstructive sleep apnea-hypopnea syndrome (OSAHS) is a sleep related breathing disorder. A popular treatment is the use of a mandibular repositioning appliance (MRA) which advances the mandibula during the sleep and decreases the collapsibility of the upper airway. The success rate of such a device is, however, limited and very variable within a population of patients. Previous studies using computational fluid dynamics have shown that there is a decrease in upper airway resistance in patients who improve clinically due to an MRA. In this article, correlations between patient-specific anatomical and functional parameters are studied to examine how MRA induced biomechanical changes will have an impact on the upper airway resistance. Low-dose computed tomography (CT) scans are made from 143 patients suffering from OSAHS. A baseline scan and a scan after mandibular repositioning (MR) are performed in order to study variations in parameters. It is found that MR using a simulation bite is able to induce resistance changes by changing the pharyngeal lumen. The change in minimal cross-sectional area is the best parameter to predict the change in upper airway resistance. Looking at baseline values, the ideal patients for MR induced resistance decrease seem to be women with short airways, high initial resistance and no baseline occlusion.     

Factors Affecting Accuracy of Data Abstracted from Medical Records

ObjectiveMedical record abstraction (MRA) is often cited as a significant source of error in research data, yet MRA methodology has rarely been the subject of investigation. Lack of a common framework has hindered application of the extant literature in practice, and, until now, there were no evidence-based guidelines for ensuring data quality in MRA. We aimed to identify the factors affecting the accuracy of data abstracted from medical records and to generate a framework for data quality assurance and control in MRA.MethodsCandidate factors were identified from published reports of MRA. Content validity of the top candidate factors was assessed via a four-round two-group Delphi process with expert abstractors with experience in clinical research, registries, and quality improvement. The resulting coded factors were categorized into a control theory-based framework of MRA. Coverage of the framework was evaluated using the recent published literature.ResultsAnalysis of the identified articles yielded 292 unique factors that affect the accuracy of abstracted data. Delphi processes overall refuted three of the top factors identified from the literature based on importance and five based on reliability (six total factors refuted). Four new factors were identified by the Delphi. The generated framework demonstrated comprehensive coverage. Significant underreporting of MRA methodology in recent studies was discovered.ConclusionThe framework generated from this research provides a guide for planning data quality assurance and control for studies using MRA. The large number and variability of factors indicate that while prospective quality assurance likely increases the accuracy of abstracted data, monitoring the accuracy during the abstraction process is also required. Recent studies reporting research results based on MRA rarely reported data quality assurance or control measures, and even less frequently reported data quality metrics with research results. Given the demonstrated variability, these methods and measures should be reported with research results.     

Spontaneous baroreflex control of heart rate during exercise and muscle metaboreflex activation in heart failure

In heart failure (HF), there is a reduced baroreflex sensitivity at rest, and during dynamic exercise there is enhanced muscle metaboreflex activation (MRA). However, how the arterial baroreflex modulates HR during exercise is unknown. We tested the hypothesis that spontaneous baroreflex sensitivity (SBRS) is attenuated during exercise in HF and that MRA further depresses SBRS. In seven conscious dogs we measured heart rate (HR), cardiac output, and left ventricular systolic pressure at rest and during mild and moderate dynamic exercise, before and during MRA (via imposed reductions of hindlimb blood flow), and before and after induction of HF (by rapid ventricular pacing). SBRS was assessed by the sequences method. In control, SBRS was reduced from rest with a progressive resetting of the baroreflex stimulus-response relationship in proportion to exercise intensity and magnitude of MRA. In HF, SBRS was significantly depressed in all settings; however, the changes with exercise and MRA occurred with a pattern similar to the control state. As in control, the baroreflex stimulus-response relationship showed an intensity- and muscle metaboreflex (MMR)-dependent rightward and upward shift. The results of this study indicate that HF induces an impairment in baroreflex control of HR at rest and during exercise, although the effects of exercise and MRA on SBRS occur with a similar pattern as in control, indicating the persistence of some vagal activity.     

Technical Critique of the Multimedia,Multipathway, Multireceptor Risk Assessment Model

The U.S. Environmental Protection Agency (USEPA) is developing the Multimedia, Multipathway, Multireceptor Risk Assessment (3MRA) model to evaluate potential human and ecological risks associated with the disposal of solid wastes designated as hazardous wastes in nonhazardous waste management units. USEPA intends to use the 3MRA model to determine national exit levels that will allow solid wastes that theoretically pose acceptable human and ecological risks to be safely managed in Subtitle D nonhazardous waste management units. We critically evaluated the 3MRA model to determine whether the methodology, interim modules, and input parameters are appropriate and scientifically defensible. Overall, our review of the 3MRA model indicates that it contains many conservative assumptions that may limit the validity of the model results and its use as a national model adequate for making regulatory decisions. Many of the assumptions and data inputs used to model the pathways involved in the transport of chemicals from a waste management unit are flawed. Other specific concerns include the lack of model validation, incompatibility of data between modules, and overestimation of potential human and ecological exposures. Before using the 3MRA model, we recommend that USEPA consider whether the 3MRA model is either an appropriate or accurate tool for evaluating the disposal of hazardous wastes nationwide.     

Application of modular response analysis to medium- to large-size biological systems

The development of high-throughput genomic technologies associated with recent genetic perturbation techniques such as short hairpin RNA (shRNA), gene trapping, or gene editing (CRISPR/Cas9) has made it possible to obtain large perturbation data sets. These data sets are invaluable sources of information regarding the function of genes, and they offer unique opportunities to reverse engineer gene regulatory networks in specific cell types. Modular response analysis (MRA) is a well-accepted mathematical modeling method that is precisely aimed at such network inference tasks, but its use has been limited to rather small biological systems so far. In this study, we show that MRA can be employed on large systems with almost 1,000 network components. In particular, we show that MRA performance surpasses general-purpose mutual information-based algorithms. Part of these competitive results was obtained by the application of a novel heuristic that pruned MRA-inferred interactions a posteriori. We also exploited a block structure in MRA linear algebra to parallelize large system resolutions.     

Non-Enhanced MR Imaging of Cerebral Aneurysms: 7 Tesla versus 1.5 Tesla

Purpose

To prospectively evaluate 7 Tesla time-of-flight (TOF) magnetic resonance angiography (MRA) in comparison to 1.5 Tesla TOF MRA and 7 Tesla non-contrast enhanced magnetization-prepared rapid acquisition gradient-echo (MPRAGE) for delineation of unruptured intracranial aneurysms (UIA).

Material and Methods

Sixteen neurosurgical patients (male n = 5, female n = 11) with single or multiple UIA were enrolled in this trial. All patients were accordingly examined at 7 Tesla and 1.5 Tesla MRI utilizing dedicated head coils. The following sequences were obtained: 7 Tesla TOF MRA, 1.5 Tesla TOF MRA and 7 Tesla non-contrast enhanced MPRAGE. Image analysis was performed by two radiologists with regard to delineation of aneurysm features (dome, neck, parent vessel), presence of artifacts, vessel-tissue-contrast and overall image quality. Interobserver accordance and intermethod comparisons were calculated by kappa coefficient and Lin''s concordance correlation coefficient.

Results

A total of 20 intracranial aneurysms were detected in 16 patients, with two patients showing multiple aneurysms (n = 2, n = 4). Out of 20 intracranial aneurysms, 14 aneurysms were located in the anterior circulation and 6 aneurysms in the posterior circulation. 7 Tesla MPRAGE imaging was superior over 1.5 and 7 Tesla TOF MRA in the assessment of all considered aneurysm and image quality features (e.g. image quality: mean MPRAGE7T: 5.0; mean TOF7T: 4.3; mean TOF1.5T: 4.3). Ratings for 7 Tesla TOF MRA were equal or higher over 1.5 Tesla TOF MRA for all assessed features except for artifact delineation (mean TOF7T: 4.3; mean TOF1.5T 4.4). Interobserver accordance was good to excellent for most ratings.

Conclusion

7 Tesla MPRAGE imaging demonstrated its superiority in the detection and assessment of UIA as well as overall imaging features, offering excellent interobserver accordance and highest scores for all ratings. Hence, it may bear the potential to serve as a high-quality diagnostic tool for pretherapeutic assessment and follow-up of untreated UIA.     

Stringent mating-type-regulated auxotrophy increases the accuracy of systematic genetic interaction screens with Saccharomyces cerevisiae mutant arrays

A genomic collection of haploid Saccharomyces cerevisiae deletion strains provides a unique resource for systematic analysis of gene interactions. Double-mutant haploid strains can be constructed by the synthetic genetic array (SGA) method, wherein a query mutation is introduced by mating to mutant arrays, selection of diploid double mutants, induction of meiosis, and selection of recombinant haploid double-mutant progeny. The mechanism of haploid selection is mating-type-regulated auxotrophy (MRA), by which prototrophy is restricted to a particular haploid genotype generated only as a result of meiosis. MRA escape leads to false-negative genetic interaction results because postmeiotic haploids that are supposed to be under negative selection instead proliferate and mate, forming diploids that are heterozygous at interacting loci, masking phenotypes that would be observed in a pure haploid double-mutant culture. This work identified factors that reduce MRA escape, including insertion of terminator and repressor sequences upstream of the MRA cassette, deletion of silent mating-type loci, and utilization of α-type instead of a-type MRA. Modifications engineered to reduce haploid MRA escape reduced false negative results in SGA-type analysis, resulting in >95% sensitivity for detecting gene–gene interactions.     

脑动静脉畸形的MRA诊断技术及诊断价值

目的:回顾性分析脑动静脉畸形(AVM)的MRA诊断方法及诊断价值。方法:51例AVM病人,男30人,女21人,年龄为9-66岁。均进行MR平扫及3D-TOF MRA或3D-PC MRA扫描。结果:MRI能清晰显示瘤巢及AVM的继发改变,MRA可基本显示AVM的全貌。结论:MRA是诊断AVM的有效方法,但常需结合DSA。     

Adrenal Vein Sampling Without Discontinuation of Mineralocorticoid Receptor Antagonist Therapy

Objective: Guidelines recommend withdrawing mineralocorticoid-receptor antagonists (MRAs) for 4 weeks prior to adrenal vein sampling (AVS), but this is not always feasible because of hypertension and hypokalemia. This retrospective study of primary aldosteronism (PA) patients who underwent AVS between 2008 and 2018 assessed the effect of continuing MRA on the AVS procedure.Methods: Clinical data including antihypertensive regimen defined by the World Health Organization Daily Defined Dose (DDD) system were collected for 19 patients with adequate cannulation and lateralization during AVS. Results were compared between 5 patients who continued and 14 patients who discontinued MRA therapy (MRA and non-MRA groups).Results: At diagnosis, plasma renin activity, plasma aldosterone concentration (PAC), potassium (K) doses, and DDD were not significantly different between groups. Aldosterone-renin ratio was significantly higher in the MRA group (median, 375.0; interquartile range [IQR], 224.8 to 544.3 vs. 148.7, 118.4 to 192.1; P = .034). No difference was found in lateralization index (median 48.3; IQR, 23.6 to 52.1 vs. 8.7; 4.9 to 20.2; P = .10). Contralateral suppression, defined as aldosterone-cortisol ratio of unaffected adrenal to periphery, trended lower in the MRA group (median, 0.17; IQR, 0.03 to 0.39 vs. 0.51; 0.27 to 1.1; P = .056). All five MRA patients underwent successful adrenalectomy with at least 50% reduction in DDD and PAC and normal K postoperatively. One MRA patient did not lateralize, which was confirmed on repeat AVS, after MRA withdrawal.Conclusion: Continuation of MRA may not interfere with AVS lateralization or affect contralateral adrenal suppression. Continuation of MRA in preparation for AVS may be considered, especially in patients with severe PA, to avoid uncontrolled hypertension and severe hypokalemia.     

Changes to the geometry and fluid mechanics of the carotid siphon in the pediatric Moyamoya disease

Background: The Moyamoya disease is a cerebrovascular disease that causes occlusion of the distal end of the internal carotid artery, leading to the formation of multiple tiny collateral arteries. To date, the pathogenesis of Moyamoya is unknown. Improved understanding of the changes to vascular geometry and fluid mechanics of the carotid siphon during disease may improve understanding of the pathogenesis, prognosis techniques and disease management. Methods: A retrospective analysis of Magnetic Resonance Angiography (MRA) images was performed for Moyamoya pediatric patients (MMD) (n = 23) and control (Ctrl) pediatric patients (n = 20). The Ctrl group was composed of patients who complained of headache and had normal MRA. We performed segmentation of MRA images to quantify geometric parameters of the artery. Computational fluid dynamics (CFD) was performed to quantify the hemodynamic parameters. Results: MMD internal carotid and carotid siphons were smaller in cross-sectional areas, and shorter in curved vascular length. Vascular curvature remained constant over age and vascular size and did not change between Ctrl and MMD, but MMD carotid siphon had lower tortuosity in the posterior bend, and higher torsion in the anterior bend. Wall shear stress and secondary flows were significantly lower in MMD, but the ratio of secondary flow kinetic energy to primary flow kinetic energy were similar between MMD and Ctrl. Conclusion: There were alterations to both the geometry and the flow mechanics of the carotid siphons of Moyamoya patients but it is unclear whether hemodynamics is the cause or the effect of morphological changes observed.     

Initial Imaging Analysis of Budd-Chiari Syndrome in Henan Province of China: Most Cases Have Combined Inferior Vena Cava and Hepatic Veins Involvement

Aim

To evaluate the type of venous involvement in Chinese Budd-Chiari syndrome (BCS) patients and the relative diagnostic accuracy of the different imaging modalities.

Methods

Using digital subtraction angiography (DSA) as a reference standard, color Doppler ultrasound (CDUS), computed tomography angiography (CTA), and magnetic resonance angiography (MRA) were performed on 338 patients with BCS. We analyzed the course of the main and any accessory hepatic veins (HVs) and the inferior vena cava (IVC) to assess the etiology of obstructed segments and diagnostic accuracy of CDUS, CTA and MRA.

Results

Among the 338 cases, there were 8 cases (2.4%) of isolated IVC membranous obstruction, 45 cases (13.3%) of isolated HV occlusion, and 285 cases (84.3%) with both IVC membranous obstruction and HV occlusion. Comparing with DSA, CDUS, CTA had a diagnostic accuracy of 89.3% and 80.2% in detecting BCS, and 83.4% of cases correctly correlated by MRA.

Conclusion

In Henan Province, most patients with BCS have complex lesions combining IVC and HV involvement. The combination of CDUS and CTA or MRI is useful for diagnosis of BCS and guiding therapy.     

Effects of isolates of ectomycorrhizal fungi and endophytic Mycelium radicis atrovirens that were dominant in soil from disturbed sites on growth of Betula platyphylla var. japonica seedlings

Effects of ectomycorrhizal fungi and endophytic Mycelium radicis atrovirens Melin (MRA) on growth of Betula platyphylla var. japonica seedlings were investigated under aseptic culture conditions. Three isolates of ectomycorrhizal fungi and two isolates of MRA were used. One MRA isolate was Phialocephala fortinii. Previous field work revealed that these isolates were dominant on the roots of B. platyphylla var. japonica seedlings grown in a mineral subsoil that had been exposed by the removal of surface soil. After a 100-day incubation, the growth of the seedlings was significantly enhanced by the colonization of these ectomycorrhizal fungal isolates as compared with uninoculated seedlings. In contrast, the growth of seedlings was retarded by the colonization of the MRA isolates. The growth of seedlings that were co-inoculated with ectomycorrhizal fungi and MRA was similar to that of uninoculated seedlings in most cases. These results suggest that ectomycorrhizal fungi have a beneficial effect on the growth of B. platyphylla var. japonica seedlings and that they suppress the deleterious effect of MRA. Thus, these ectomycorrhizal fungi probably have an important role in establishing B. platyphylla var. japonica seedlings during the initial stage of re-vegetation following site disturbance by the removal of surface soil.     

Quantification of Blood Flow in Internal Cerebral Artery by Optical Flow Method on Digital Subtraction Angiography in Comparison with Time-Of-Flight Magnetic Resonance Angiography

Objective

This study compared data on the blood flow velocity in the internal carotid artery, which was obtained using the optical flow method (OFM) with digital subtraction angiography (DSA) and the time-of-flight (TOF) technique using magnetic resonance angiography (MRA).

Materials and Methods

Images were obtained from 12 cerebrovascular patients who underwent both brain DSA and MRA imaging. The OFM was applied on the DSA images to determine the average blood flow velocity. The calculated results were compared with the values obtained from the TOF-MRA data. A linear fit was performed on the data and Bland-Altman plots were analyzed.

Results

The blood flow velocity was closely associated with vascular diseases. Color-coding of the OFM measurements were superimposed on to the DSA images, which quantitatively illustrated the relative flow in the vessels. The average blood flow velocity was calculated using OFM and DSA, which demonstrated a high correlation with the MRA measurements in the anterior-posterior (AP) view (R = 0.71). In contrast, the average blood flow velocity was low in the lateral view (R = 0.28). The consistency between the high and low blood velocity in the AP view was better compared to the lateral view. The blood flow velocity distribution in the AP view was statistically closer to the MRA measurement compared to the lateral view.

Conclusions

This study evaluated the correlation of blood flow measured using DSA and TOF-MRA in a small heterogeneous group of patients with cerebrovascular lesions. OFM with DSA imaging reveals hemodynamic information and TOF-MRA.     

Use of acute phenolic denervation to show the neuronal dependence of Ca2+-induced relaxation of isolated arteries

We recently showed that perivascular sensory nerves of mesenteric resistance arteries (MRA) express a receptor for extracellular Ca2+ (CaR) and proposed that activation of the CaR by Ca2+ causes nerve-dependent vascular relaxation. We now describe a novel procedure for acutely denervating isolated arteries and have used this method to test the hypothesis that Ca2+-induced relaxation of MRA is nerve dependent. MRA were studied using a wire myograph equipped with electrodes for electrical field stimulation (EFS) which caused sympathetic nerve-mediated contraction, and when applied in the presence of guanethidine, induced nerve-mediated relaxation. Ca2+-induced relaxation was produced by the cumulative addition of Ca2+ to MRA precontracted with norepinephrine. Exposure of MRA to 6.5% phenol in ethanol for 20 sec significantly attenuated EFS-induced contraction and relaxation, and Ca2+-induced relaxation. The magnitude of the relaxation response to EFS correlated significantly with the decrease in Ca2+-induced relaxation. In contrast, endothelium-dependent relaxation induced by acetylcholine was slightly, but nonsignificantly decreased by phenol treatment and did not correlate with Ca2+-induced relaxation. These data indicate that brief exposure of isolated MRA to phenol significantly impairs perivascular nerve function and support the hypothesis that Ca2+-induced relaxation is neurally mediated.     

A meta-analysis of the life cycle greenhouse gas balances of microalgae biodiesel

Purpose

Microalgae biodiesel has attracted considerable attention as a potential substitute for fossil fuels and biodiesel from food crops. Nevertheless, its reported climate impacts in the scientific literature vary significantly. This article describes and synthesizes the range of results found in the life cycle assessment (LCA) literature regarding microalgae biodiesel studies to investigate whether particular parameters, e.g. technologies, were associated with higher or lower greenhouse gas (GHG) emissions so that a best practice can be inferred from currently available LCA data and thereby recommended.

Methods

A systematic literature review and meta-regression analysis (MRA) of 36 LCA studies that report on the GHG emissions of microalgae biodiesel was conducted. An assessment of key aspects, including modelling choices and technologies, was performed. Furthermore, MRA models were formulated considering several variables of interest describing both technical and modelling choices to identify the main causes for the variability in GHG emissions per MJ of biodiesel. Variables chosen include: microalgae species; culture medium; cultivation system; source of CO₂; extraction technology; conversion technology; system boundary; geographical scope; inclusion or exclusion of capital goods; and how multifunctionality was handled.

Results and discussion

The reviewed studies altogether reported 308 results ranging from ?0.7 to 3.8 kg CO₂ eq. MJ^?1_biodiesel, portraying 19 different system configurations. Despite the comprehensive range of variables assessed, the models generated could not plausibly explain that the variability in GHG emissions depends either on the technologies considered or on the methodological choices adopted. However, the following relationships could be observed: location in Europe and high oil productivity were associated with lower emissions, whilst dry extraction should be avoided for leading to higher GHG emissions, on average.

Conclusions

There is a large degree of variability within the technologies considered, as well as the methodological choices adopted, so that no robust conclusions could be drawn from the MRA. Notwithstanding, average GHG emissions reported were more than twice as high as fossil diesel and, while there are some studies showing large benefits, none of the various algae technologies performed consistently better than fossil diesel, questioning the climate-mitigation potential of microalgae biodiesel.

     

Rectus abdominis activity,but not femoris,is similar in different core training exercises: A statistical parametric mapping analysis

Rectus abdominis (RA) and rectus femoris (RF) differently activate in hip and trunk flexion movements. Previous studies using surface electromyography (sEMG) showed heterogenous results in mean and maximum activity of Upper (URA), Middle (MRA), and Lower (LRA) RA. Statistical Parametric Mapping (SPM) and Time-Varying Multi-muscle Co-activation function (TMCf) are emerging methods for whole-time-course continuous comparisons of muscle activity and co-activation. The aim was to analyse RA and RF activity in three core training exercises with continuous approach. Eight subjects performed Curl-up, Sit-up 45° and Sit-up 90° (where 45° is half and 90° is complete trunk flexion). sEMG from URA, MRA, LRA and RF were normalized to the maximum voluntary contraction root-mean-square (RMS_MVC), and compared among muscles/exercises with SPM and TMCf. Angular displacement was assessed using stereophotogrammetry. Curl-up, Sit-up 45° and Sit-up 90° did not differently activate URA, MRA or LRA, and in their common range of motion (ROM) RA activity was similar among the three exercises. Conversely, Sit-up exercises elicited higher RF activity than Curl-up (on average 45% vs. 25% RMS_MVC) mainly due to the wider ROM. RA-RF co-activation pattern was different in concentric and eccentric phases between Sit-up exercises and Curl-up, leading to significantly higher co-activation in Sit-up exercises.     

Cells with marrow and spleen repopulating ability and forming spleen colonies on day 16, 12, and 8 are sequentially ordered on the basis of increasing rhodamine 123 retention

Mouse bone marrow cells (BMC) were subjected to countercurrent centrifugal elutriation and subsequently separated on the basis of light scatter and fluorescence intensity after being labeled with the supravital dye Rhodamine 123 (Rh-123). The sorted cells were then assayed for their in vivo spleen colony-forming ability (day -8, -12, and -16 CFU-S) and their ability to repopulate the bone marrow or spleen over a 13-day period with CFU-S-12, CFU-GM, or nucleated cells. Cells with marrow repopulating ability (MRA), as measured by the ability of the sorted cells to repopulate the marrow with secondary CFU-S-12 or CFU-GM, had low affinity for Rh-123. These cells showed minimal spleen colony-forming ability, and the ratio of MRA to CFU-S-12 in this preparation was 309. Cells with spleen repopulating ability (SRA), CFU-S-16, CFU-S-12, and CFU-S-8 retained increasing amounts of Rh-123, respectively, and CFU-S-8 were almost exclusively found among cells with high Rh-123 affinity. These cells also included about half of all day-12 CFU-S, and the ratio of MRA to day-12 CFU-S was 0. The results show that MRA cells, SRA cells, CFU-S-16, CFU-S-12, and CFU-S-8 can be sequentially ordered on the basis of increasing mitochondrial activity. The data also demonstrate for the first time, and without the application of negative selection by the use of cytostatic agents, that MRA cells are a separate class of primitive hemopoietic stem cells that fully meet the criteria of pre-CFU-S.     

Quantitative Amyloid Imaging Using Image-Derived Arterial Input Function

Amyloid PET imaging is an indispensable tool widely used in the investigation, diagnosis and monitoring of Alzheimer’s disease (AD). Currently, a reference region based approach is used as the mainstream quantification technique for amyloid imaging. This approach assumes the reference region is amyloid free and has the same tracer influx and washout kinetics as the regions of interest. However, this assumption may not always be valid. The goal of this work is to evaluate an amyloid imaging quantification technique that uses arterial region of interest as the reference to avoid potential bias caused by specific binding in the reference region. 21 participants, age 58 and up, underwent Pittsburgh compound B (PiB) PET imaging and MR imaging including a time-of-flight (TOF) MR angiography (MRA) scan and a structural scan. FreeSurfer based regional analysis was performed to quantify PiB PET data. Arterial input function was estimated based on coregistered TOF MRA using a modeling based technique. Regional distribution volume (V_T) was calculated using Logan graphical analysis with estimated arterial input function. Kinetic modeling was also performed using the estimated arterial input function as a way to evaluate PiB binding (DVR_kinetic) without a reference region. As a comparison, Logan graphical analysis was also performed with cerebellar cortex as reference to obtain DVR_REF. Excellent agreement was observed between the two distribution volume ratio measurements (r>0.89, ICC>0.80). The estimated cerebellum V_T was in line with literature reported values and the variability of cerebellum V_T in the control group was comparable to reported variability using arterial sampling data. This study suggests that image-based arterial input function is a viable approach to quantify amyloid imaging data, without the need of arterial sampling or a reference region. This technique can be a valuable tool for amyloid imaging, particularly in population where reference normalization may not be accurate.     

Progression of central nervous system disease from pediatric to young adulthood in sickle cell anemia

Silent cerebral infarcts and arteriopathy are common and progressive in individuals with sickle cell anemia. However, most data describing brain lesions in sickle cell anemia are cross-sectional or derive from pediatric cohorts with short follow-up. We investigated the progression of silent cerebral infarct and cerebral vessel stenosis on brain MRI and MRA, respectively, by describing the incidence of new or worsening lesions over a period of up to 25 years among young adults with sickle cell anemia and explored risk factors for progression. Forty-four adults with sickle cell anemia (HbSS or HbSβ⁰thalassemia), exposed to chronic transfusions (n = 12) or hydroxyurea (n = 32), median age 19.2 years (range 18.0–31.5), received a screening brain MRI/MRA and their results were compared with a clinical exam performed during childhood and adolescence. We used exact log-rank test to compare MRI and MRA progression among any two groups. The hazard ratio (HR) and 95% confidence interval (CI) were calculated from Cox regression analyses. Progression of MRI and MRA occurred in 12 (27%) and 4 (9%) young adults, respectively, relative to their pediatric exams. MRI progression risk was high among participants with abnormal pediatric exams (HR: 11.6, 95% CI: 2.5–54.7) and conditional or abnormal transcranial Doppler ultrasound velocities (HR: 3.9, 95% CI: 1.0–15.1). Among individuals treated with hydroxyurea, high fetal hemoglobin measured in childhood was associated with lower hazard of MRI progression (HR: 0.86, 95% CI: 0.76–0.98). MRA progression occurred more frequently among those with prior stroke (HR: 8.6, 95% CI: 1.2–64), abnormal pediatric exam (P = 0.00084), and elevated transcranial Doppler ultrasound velocities (P = 0.004). Brain MRI/MRA imaging in pediatrics can identify high-risk patients for CNS disease progression in young adulthood, prompting consideration for early aggressive treatments.