Magnetic Resonance Imaging Research Articles

Extra-cellular volume fraction analysis on cardiac CT is useful for predicting the prognosis of hypertrophic cardiomyopathy

Abstract Introduction Extra-cellular volume (ECV) fraction on magnetic resonance imaging (MRI) can evaluate the degree of myocardial fibrosis and has been reported to help diagnose and evaluate the prognosis of cardiomyopathy. In hypertrophic cardiomyopathy (HCM), ECV analysis on MRI is reported to help predict ventricular arrhythmias. However, the performance of cardiac MRI takes time, and there are also several contraindications. Cardiac computed tomography (CT) is more versatile than cardiac MRI and is also useful in screening coronary artery disease. ECV analysis on CT is now available, and a good correlation with ECV on MRI has been reported. We hypothesized that ECV on CT, a new fibrosis indicator, would be useful in predicting prognosis in HCM patients. Purpose To determine the utility of ECV analysis on CT to predict the prognosis in patients with HCM. Methods One hundred and three HCM patients (68 males, 66 ± 11 years old) who underwent cardiac CT using 320-row detector CT or 256-row detector CT, from 2008 to 2021 at our two hospitals were analyzed. We measured left ventricular (LV) ECV (LV-ECV) on CT and collected patient characteristics, transthoracic echocardiographic, and other CT findings. We investigated the relationship between these findings and the major adverse cardiac events (MACEs) (cardiac death, fatal arrhythmia, and heart failure hospitalization) after CT. Results All patients were followed for 64 ± 54 months after cardiac CT, and 15 patients (14.6%) had MACEs (ten heart failure hospitalization cases, two ventricular fibrillation cases, two sustained ventricular tachycardia cases, and one sudden cardiac death case). The patients with MACEs had a significantly higher LV-ECV, sudden cardiac death (SCD) risk score and lower LV ejection fraction (LVEF) than those without MACEs（42.0 ± 8.3% vs. 33.7 ± 6.1%, P < 0.001, 2.4 ± 0.39 vs 1.95 ± 0.16, P= 0.047, and 57.7 ± 11.9% vs. 66.7 ± 6.9%, P = 0.004). The percentage of dilated phase HCM was significantly higher in the patients with MACEs than those without MACEs (21% vs 0%, p=0.002). LV-ECV was the only significant predictor of MACEs based on the multivariate analysis by Cox proportional hazard model (hazard ratio 1.23, 95% confidence interval 1.09-1.41, P<0.001). The optimal threshold of LV-ECV to predict MACEs was 37.6% based on the receiver operating characteristic analysis. The sensitivity and specificity of LV-ECV to predict MACEs were 73% and 78% at the best cut-off, and the area under the curve was 0.79 (Figure A). The patients with LV-ECV ≥ 37.6% (30 patients) had significantly higher MACEs than those with LV-ECV < 37.6% during the follow-up periods (P < 0.001) (Figure B). Conclusion LV-ECV on CT of 37.6% is a good prognostic indicator in HCM cases. ECV analysis on CT helped predict MACEs in HCM cases.

Altered cerebral oxygen extraction and metabolism in preterm neonates and the relationship to anemia: A noncontrast MRI study

AbstractObjectiveThe preterm brain is susceptible to structural injuries, which may be related to an imbalance between blood supply and oxygen metabolism. However, the effect of preterm birth on cerebral oxygen metabolism and its underlying mechanism have not been fully elucidated. The present study measured cerebral oxygen extraction and metabolism using noncontrast magnetic resonance imaging (MRI) methods in preterm neonates and examined its relationship with anemia of prematurity.MethodsFifty neonates with a gestational age of 28–42 weeks were enrolled. Cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) were measured with T2‐relaxation‐under‐spin‐tagging (TRUST) MRI, together with cerebral blood flow (CBF).ResultsWe showed that CBF (p = 0.00021) and CMRO2 (p < 0.0001) increased with gestational age while OEF increased with postnatal age (p = 0.0013). Higher OEF was also associated with a higher Apgar score at birth (p = 0.039). Furthermore, hematocrit significantly mediates the increase of OEF with postnatal age (p < 0.001). Structural equation modeling analysis suggested a bidirectional relationship between CBF and CMRO2; both contributed to the changes in OEF.InterpretationThese findings demonstrated an altered cerebral oxygen metabolism in preterm brain, suggesting a potential role of MRI–based oxygenation measurement in the assessment of transfusion and intervention for preterm neonates.

Assessment of meniscal extrusion with ultrasonography: a systematic review and meta-analysis

BackgroundMagnetic resonance imaging (MRI) is the imaging of choice for meniscal extrusion (ME). However, they may underappreciate the load-dependent changes of the meniscus. There is growing evidence that weight-bearing ultrasound (WB US) is more suitable, particularly in revealing occult extrusion. We therefore perform a systematic review and meta-analysis on the validity and reliability of US in diagnosing extrusion. Furthermore, we explored whether it detects differences in extrusion between loaded and unloaded positions and those with pathological (osteoarthritis and meniscal injury) and healthy knees.MethodsThe Cochrane Controlled Register of Trials, PubMed, Medline, and Embase were used to perform a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Data pertaining to intra- and interrater reliability of US in measuring meniscal extrusion (ME), its correlation with magnetic resonance imaging (MRI), and head-to-head comparison of potential factors to influence ME were included [loading versus unloading position; osteoarthritis (OA) or pathological menisci (PM) versus healthy knees; mild versus moderate–severe knee OA]. Pooled data were analyzed by random or fixed-effects models.ResultsA total of 31 studies were included. Intraclass correlation coefficients (ICC) for intra- and interrater reliability were minimum 0.94 and 0.91, respectively. The correlation between US and MRI was (r = 0.76). US detected ME to be greater in the loaded position in all knees (healthy, p < 0.00001; OA, p < 0.00001; PM, p = 0.02). In all positions, US detected greater extrusion in OA (p < 0.0003) and PM knees (p = 0.006) compared with healthy controls. Furthermore, US revealed greater extrusion in moderate–severe OA knees (p < 0.00001).ConclusionsThis systematic review suggests ultrasonography can play an important role in the measurement of meniscal extrusion, with results comparable to that of MRI. However, to what extent it can differentiate between physiological and pathological extrusion requires further investigation, with an absolute cutoff value yet to be determined. Nevertheless, it is an appropriate investigation to track the progression of disease in those with meniscal pathologies or osteoarthritis. Furthermore, it is a feasible investigation to evaluate the meniscal function following surgery.Level of evidence: IV, Systematic review of level III–IV evidence.

Extra cellular volume by computed tomography is useful for prediction of prognosis in cardiac sarcoidosis

Abstract Background Extracellular volume (ECV) fraction on magnetic resonance imaging (MRI) has been useful in evaluating the degree of myocardial fibrosis and has been reported to help diagnose and evaluate the prognosis of cardiomyopathy. However, there are also several contraindications in the cardiac MRI, and the performance of it takes time. Computed tomography (CT) helps screen for coronary artery disease, is more versatile than cardiac MRI, and is also useful in screening for coronary artery disease. Myocardial extracellular volume (ECV) analysis on CT has been recently eligible and has shown a good correlation with ECV on MRI. We hypothesized that ECV on CT, a new fibrosis indicator, would be useful in predicting prognosis in patients with cardiac sarcoidosis (CS). Purpose The purpose of this study is to evaluate the utility of ECV analysis on CT for predicting major adverse cardiac events (MACEs) in cases with cardiac sarcoidosis (CS). Methods As a single-center study, 48 patients (18 males, 67 ± 11 years old) diagnosed with CS based on the 2016 Japanese Circulation Society criteria and who underwent cardiac CT using 320-row detector CT or 256-row detector CT, and including late-phase images from December 2008 to January 2024 were analyzed retrospectively. We evaluated the ECV of left ventricular myocardium (LVM) using commercially available software (Figure A). The primary endpoint was MACEs, a composite of all-cause death, heart failure hospitalization, and fatal ventricular arrhythmia. Results Among all 48 patients, 14 combined events (10 fatal ventricular arrhythmias, three heart failure hospitalizations, and one all-cause death) were observed during a follow-up of 56 ± 57 months. ECV of LVM on CT was significantly higher in patients with MACEs than the others (37 ± 5.6% vs 33 ± 4.6%, P = 0.0087). The best cut-off value of ECV of LVM on CT for prediction of MACEs was 34.97%, and the sensitivity and specificity of LV-ECV to predict MACEs were 71% and 76% at the best cut-off, and the area under the curve was 0.73 based on the receiver operating characteristics curve analysis (P = 0.009) (Figure B). The cases with ECV ≥ 34.97% (n = 18) had significantly higher MACEs than the cases with ECV &amp;lt; 34.97% based on the Kaplan-Meier analysis (P = 0.0031) (Figure C). In the multivariate Cox proportional hazard model, ECV on LVM (Hazard ratio 1.11, 95% confidence interval 1.00-1.21, p=0.0493) and history of VT ablation (Hazard ratio 27.7, 95% confidence interval 4.27-180, p=0.0011) were the significant predictors of MACEs. Conclusion Adverse events mainly caused by fatal ventricular arrhythmia are relatively common in CS. Evaluation of ECV by CT may be useful for the prediction of MACEs in cases with CS.

Validation of fat mass metrics in pediatric obesity

Introduction Hudda-Index is a prediction model for fat mass (FM) based on simple anthropometric measures., FM is a crucial factor in the development of comorbidities, i.e., type 2 diabetes. Hence, Hudda-Index is a promising tool to facilitate identification of children at risk for metabolic comorbidities. It has been validated against deuterium dilution assessments, however, independent validation against the gold-standard for body composition analysis, magnetic resonance imaging (MRI), is lacking. The aim of this study is to validate FM calculated by Hudda-Index against FM measured by MRI. The secondary aim is to compare Hudda-Index to other anthropometric measures including body mass index (BMI), BMI-standard deviation score (BMI-SDS), waist/hip-ratio, waist circumference (WC) and skinfold thickness. Methods The study cohort consists of 115 individuals between the age of 9 and 15 years, recruited at Paracelsus Medical University Hospital in Salzburg (Austria) and Uppsala University Children's Hospital (Sweden). Anthropometry, blood samples, and oral glucose tolerance tests followed standard procedures. MRI examinations were performed to determine visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Results BMI and WC showed slightly stronger associations with the reference standard VAT (r=0.72 and 0.70, p&lt;0.01, respectively) than Hudda-Index (r= 0.67, p&lt;0.01). There is an almost perfect linear association between BMI and Hudda-Index. Accordingly, BMI and Hudda-Index both showed an acceptable association with cardiometabolic parameters. VAT was strongly associated with markers of liver status (LFF r=0.59, p&lt;0.01) and insulin resistance (HOMA-IR r=0.71, p&lt;0.01) and predicted metabolic dysfunction-associated steatotic liver disease (MASLD). Conclusion BMI, although an imperfect measure, remains the most reliable tool and estimates cardiometabolic risk more reliably than other anthropometry-based measures.

High physical activity relates to higher risk of incident carotid plaque components

Abstract Background The rupture of carotid atherosclerotic plaque, primarily driven by plaque components, is among the leading causes of ischemic stroke. Although physical activity (PA) stands as a major modifiable target for prevention of atherosclerotic diseases, recent studies suggested a potential adverse impact of high-volume PA on atherosclerotic plaque burden in athletes. Data remains scarce from the community-dwelling population regarding to the impact of PA on the longitudinal change of carotid plaque components. Objectives To assess the association between PA and the incidence of carotid plaque components and explore whether the association of PA with stroke and all-cause mortality differs by the presence of plaque components. Methods Between 2007 and 2012, in a community- dwelling cohort in Netherlands, 1327 stroke-free persons (mean ± standard deviation age 72 ± 9 years, 45% women) with carotid atherosclerosis (carotid intima-media thickness &amp;gt; 2.5 mm) were invited for magnetic resonance imaging (MRI) to assess carotid plaque components. From these, 696 persons (1267 carotid arteries) underwent a follow-up MRI between 2014 and 2017 (median between-scan interval 6 years). Carotid plaque components included calcification, intraplaque hemorrhage (IPH), and lipid-rich necrotic core (LRNC). The volume of moderate, vigorous and total PA (unit: metabolic equivalent task hour, MET-h) was assessed using LASA Physical Activity Questionnaires around the time of the first MRI scan. Participants were followed for the occurrence of stroke or all-cause mortality until December 31, 2019. Generalized estimation equation and Cox regression models were used in the analyses, with adjustments for plaque size and other cardiovascular risk factors. Results Compared to lowest quintile PA group, participants in the highest quintile total PA group had a higher risk of new onset of plaque components, odds ratio (95%CI) 2.69 (1.21; 5.94) for calcification, 1.35 (0.82; 2.24) for LRNC and 1.93 (1.12; 3.34) for IPH (Figure 1). Similar associations were observed for vigorous PA but not for moderate PA. Over a median follow-up of 9.5 years, 118 persons suffered a stroke and 298 died. As shown in table 1, baseline IPH, rather than LRNC or calcification, modulated the associations of PA with stroke and all-cause mortality (P-interaction &amp;lt;0.05): higher total PA was associated with a lower risk of stroke among IPH-free persons, with the hazard ratio (95% CI) of 0.929 (0.867; 0.996) per 10 MET-h/week increase; no associations between PA and stroke were found among those with IPH. Similar associations were found between vigorous PA and all-cause mortality. Conclusions Among the middle-aged and elderly with subclinical atherosclerosis, high level PA, especially high vigorous PA, may lead to an unstable carotid plaque. The beneficial effect of PA on stroke and all-cause mortality is only among persons with a stable carotid plaque profile, especially without IPH.

Basal inferior-septal segment is highly susceptible to deformation in the clinical spectrum of transthyretin-derived cardiomyopathy

Abstract Background The prevalence of transthyretin-derived cardiomyopathy (ATTR-CM) is increasing; however, understanding the morphological and functional manifestations within the left ventricle (LV) across the spectrum of heart failure (HF) remain limited. Purpose This study aims to assess the longitudinal strain (LS) using 2D speckle-tracking echocardiography in ATTR-CM patients and compared them with the features of magnetic resonance imaging (MRI). Methods 2D speckle-tracking echocardiography evaluated LS in 63 histology-confirmed ATTR-CM patients (median age: 78 years; male: 94%), with and without developing HF. Additionally, native T1 and extracellular volume (ECV) measured using MRI were compared with LS in 18-segments depicted on a Bull’s eye plot. Results Patients were grouped based on HF status: Group 1 (no HF symptoms, n=10), Group 2 (HF with preserved LV ejection fraction (LVEF), n=17), and Group 3 (reduced LVEF, n=36). Group 3 exhibited higher levels of brain natriuretic peptide and troponin T, and lower estimated glomerular filtration rate, compared with Group 1 and 2. Echocardiography revealed heightened LV thickness and decreased LVEF in Group 3. LS analysis revealed susceptibility to deformation in the basal inferior-septal segment, persisting even in Group 1. MRI revealed a high average native T1 level with minimal standard deviation (indicative of tissue homogeneity). However, this level increased as distance from the inferior-septal segment grew in the basal and mid-ventricular slices. Contrast images displayed maximal ECV in the basal and mid-ventricular inferior-septum, a phenomenon persisting in Group 1. Segmental LS decline, as assessed by echocardiography, correlated with ECV expansion but not with native T1 values. Conclusion 2D speckle-tracking echocardiography can identify segmental LS impairment in ATTR-CM patients, potentially reflecting amyloid burden and fibrosis extent. Our data suggest that amyloid deposition might be widespread from the basal inferior-septal segment to other areas.

Initial results of the Hyperion IIDPET insert for simultaneous PET-MRI applied to atherosclerotic plaque imaging in New-Zealand white rabbits.

In preclinical research, in vivo imaging of mice and rats is more&#xD;common than any other animal species, since their physiopathology is very well-&#xD;known and many genetically altered disease models exist. Animal studies based on&#xD;small rodents are usually performed using dedicated preclinical imaging systems&#xD;with high spatial resolution. For studies that require animal models such as mini-&#xD;pigs or New-Zealand White (NZW) rabbits, imaging systems with larger bore&#xD;sizes are required. In case of hybrid imaging using Positron Emission Tomography&#xD;(PET) and Magnetic Resonance Imaging (MRI), clinical systems have to be used,&#xD;as these animal models do not typically fi t in preclinical simultaneous PET-MRI&#xD;scanners.&#xD;Approach. In this paper, we present initial imaging results obtained with the&#xD;Hyperion IID PET insert which can accommodate NZW rabbits when combined&#xD;with a large volume MRI RF coil. First, we developed a rabbit-sized image&#xD;quality phantom of comparable size to a NZW rabbit in order to evaluate the&#xD;PET imaging performance of the insert under high count rates. For this phantom,&#xD;radioactive spheres with inner diameters between 3.95 and 7.86 mm were visible&#xD;in a warm background with a tracer activity ratio of 4.1 to 1 and with a total&#xD;18-F activity in the phantom of 58MBq at measurement start. Second, we performed&#xD;simultaneous PET-MR imaging of atherosclerotic plaques in a rabbit in vivo using&#xD;a single injection containing 18-F-FDG for detection of infl ammatory activity,&#xD;and Gd-ESMA for visualization of the aortic vessel wall and plaques with MRI.&#xD;Main results. The fused PET-MR images reveal 18-F-FDG uptake within an&#xD;active plaques with plaque thicknesses in the sub-millimeter range. Histology&#xD;showed colocalization of 18-F-FDG uptake with macrophages in the aortic vessel wall lesions. &#xD;Significance. Our initial results demonstrate that this PET insert&#xD;is a promising system for simultaneous high-resolution PET-MR atherosclerotic&#xD;plaque imaging studies in NZW rabbits.

Identification of new instances of white matter hyperintensities in patients following TAVI (from the CAPITA study)

Abstract A third of patients diagnosed with symptomatic severe aortic valve stenosis and scheduled for transcatheter aortic valve implantation (TAVI) exhibit some level of cognitive impairment. The prospective CAPITA study aimed to systematically evaluate the impact of TAVI on cerebral and cognitive outcomes in patients undergoing the procedure. In this report, we focus on the identification of new incidence of white matter hyperintensities (WMH) and the correlation with changes in cognitive functioning. The CAPITA (CArdiac OutPut, Cerebral Blood Flow and Cognition In Patients With Severe Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation) study is a prospective study of cerebral and cognitive outcomes following TAVI. Patients underwent magnetic resonance imaging (MRI) and extensive neuropsychological testing at baseline and three month follow-up. New cerebral infarcts were defined according to NeuroARC criteria. We examined the incidence of new WMH in terms of volume (Δ mL) and number on FLAIR MRI, and explored the correlation between new WMH and cognitive functioning. A total of 148 patients were included who underwent TAVI between August 2020 and October 2022. Mean age was 80.5±5.7 years, of whom 43% female with a median STS-PROM of 2.0% (IQR 1.4%-2.9%). Median baseline WMH comprised 127 (IQR 32-216) lesions, with a total volume of 13.1 (IQR 7.0-24.6) mL. At 3 months follow-up, the number of lesions increased to 164 (IQR 121-301) lesions, with a total volume of 13.3 (IQR 5.8-21.5) mL. Median WMH volume increase was 0.1 (IQR 0.0-0.3) ml (p=0.02). A total of 9 patients (9.5%) had an increase of 1 mL of WMH or more. At follow-up, 12% of patients exhibited cognitive decline of &amp;gt;0.5SD. These patient tended to have a greater increase in white matter hyperintensity volume (1.26±2.96 ml), compared to the 53% of patients with stable cognition (0.29±0.45 ml) and the 36% of patients with improved cognition (0.31±0.91 ml), (p=0.06). WMH lesions did not exhibit distribution patterns across various locations within the groups characterized by declined, stable, or improved cognition (Figure 1). WMH volumes were higher in patients who experienced postprocedural delirium than in patients without delirium (27.1±14.0 vs 15.0±12.5 mL, p&amp;lt;0.001). In this study, patients with severe symptomatic aortic valve stenosis undergoing TAVI, there was an overall increase of white matter hyperintensity volume between baseline and 3-month follow-up. Up to 12% of patients had cognitive decline, which was associated with new white matter hyperintensities on MRI.

Large sample size MRI measurements to assess the relation between cardiac function and structure and white matter hyperintensity volumes

Abstract Background People with established cardiovascular disease (CVD) are at risk of early cognitive decline, and neurological diseases such as dementia. CVD and neurological diseases share common risk factors, such as blood pressure, sedentary lifestyle, as well as genomic risk factors such as mutations in APOE4 [1]. It's unclear to what extent the co-occurrence of CVD and neurological diseases is explained by these risk factors, or whether there is a direct association where CVD is a first step towards poorer neurological health. White matter hyperintensities (WMH) of presumed vascular origin are damaged areas in the brain observed through magnetic resonance imaging (MRI). These lesions are associated with progressive neurological disease such as vascular dementia, as well with risk factors for CVD [2]. Purpose We set out to determine to what extent CMR measurements associated with WMH independent of known cerebrovascular risk factors. Methods Cardiac and brain MRI images were analysed for 23,963 UK biobank (UKB) participants. WMH analysis included 5 brain regions (Frontal[F], Parietal[P], Temporal[T], Occipital[O], Basal Ganglia and Thalami [BGT]) and total brain WMH volume. Cardiac traits included stroke volumes, atrial volumes, ejection fractions of right and left chambers, left ventricular (LV) strain, LV wall thickness and aortic areas. Multivariable regression analysis was carried out, where each cardiac trait was regressed on each brain region and adjusted for: age, difference between age at initial visit and imaging visit, sex, systolic and diastolic blood pressure, Hba1c, household income, educational status, Townsend score and family history of disease (Alzheimer’s, Parkinson's, high blood pressure, stroke, heart disease) . Results were evaluated against a multiple testing correct p-value threshold of 0.05, reflecting the number of principle components(n=10) necessary to explain 90% of the cardiac trait variability. Results For 5 cardiac traits (right ventricular stroke volume, left atrial stroke volume, left ventricular stroke volume, left ventricular ejection fraction and right ventricular end diastolic volume) higher values were associated with lower WMH volumes in all brain regions. Additionally, some cardiac traits such as LV cardiac output associated with specific brain regions (T, O, BGT). Additionally, APOE- ε4 stratified analyses indicated, homozygous carriers show a greater association between higher minimum LA and RA volumes and higher WMH volumes in the occipital lobe. Conclusions This study gives an insight into the WMH burden in a large population of adults. It highlights the associations of cardiac traits with white matter hyperintensity volumes in different brain regions independent of known risk factors. Using cardiac traits as surrogate markers of different cardiac disease could explain how cardiac functionality defines WMH volume distribution and subsequently the wider relationship between CVD and cerebrovascular disease.Figure 1Graphical Abstract

Brainstem changes causing reversible RBD in patients with spontaneous intracranial hypotension: a longitudinal neuroimaging study.

This study aimed to investigate the prevalence of REM sleep behavior disorder (RBD) in patients with spontaneous intracranial hypotension (SIH) and longitudinally assess the effects of epidural blood patch (EBP) treatment on brainstem structures using a neuroimaging approach. Twenty-two participants (10 SIH patients and 12 controls) underwent 3-Tesla Magnetic Resonance Imaging (MRI) scans. Midbrain and pons areas were measured on T1-weighted scans at baseline in both groups and three months after the first EBP in SIH patients to determine any MRI structural changes. The RBD Single-Questionnaire was used to screen SIH patients with symptoms suggestive of RBD for polysomnographic (PSG) recording. Half of the SIH patients (5/10) exhibited PSG-confirmed RBD. Baseline evaluation revealed deep brain swelling (DBS) on MRI scans in SIH-RBD patients. Following EBP treatment, significant changes in midbrain and pons morphometry were associated with complete clinical remission of RBD. Cross-sectional analysis showed larger midbrain and pons areas in SIH patients (with and without RBD) compared to controls. A midbrain area of 200 mm2 was identified as a cut-off value distinguishing SIH patients (with and without RBD) from controls individually. Longitudinal analysis demonstrated lower midbrain areas at follow-up compared to baseline in SIH patients. The study suggests that brainstem morphometric changes may underlie reversible RBD in SIH patients. Midbrain area measurement could serve as a dynamic biomarker for SIH, particularly in the presence of RBD, offering insights for clinical practice.

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 &amp;gt;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.

Extracellular volume analysis on cardiac computed tomography is useful to predict prognosis after cardiac resynchronization therapy

Abstract Background Left-ventricular (LV) extracellular volume (ECV) (LVECV) is often evaluated on magnetic resonance imaging (MRI), and the value is well correlated with biopsy-identified myocardial fibrosis. Recently, mechanical development has been achieved, and ECV analysis on cardiac computed tomography (CCT) has been eligible using the latest software, and the ECV on CCT is well correlated with the ECV on MRI. Cardiac resynchronization therapy (CRT) has been usually performed in cases with severe heart failure, but almost 30 percent of them are non-responders. Therefore, the indicators to predict non-responders to cardiac resynchronization therapy (CRT) have been sought in advance. Purpose The purpose of this study is to reveal the utility of LVECV on CCT for the prediction of patient prognosis in the candidates of cardiac resynchronization therapy (CRT) who have low LV function. Methods We analyzed 53 patients (30 males, 65 ± 14 years old) with heart failure who underwent CCT, including late phase scan, using 320-row detector CT (Aquilion One or Aquilion One ViSion Edition, Cannon Medical Systems) or 256-row detector CT (Revolution CT Apex, GE Healthcare), before the implantation of a CRT device from December 2008 to January 2024. The primary outcomes were defined as cardiac death, hospitalization due to HF, and fatal arrhythmia after CRT implantation. CRT responders were defined as the patients whose LV endo-systolic volume was decreased by 15% or more on transthoracic echocardiography. Results Twenty-two patients (42%) had primary outcomes (10 cardiac death, 7 fatal arrhythmia, 5 hospitalization due to HF). LVECV was lower in CRT responder (n = 23) than the others (n = 25) (35 ± 6.3% vs 41 ± 6.8%, P = 0.006). LVECV was higher in the patients with primary outcomes (n = 22) than the others (n = 31) (35 ± 5.0% vs 41 ± 7.8%, P = 0.019). Based on the receiver-operating characteristics curve analysis, the best cut-off of LVECV for predicting primary outcomes was 44.03% (B). In the survival analysis using the Cox proportional hazard model, LVECV on CCT was a significant predictor of primary outcomes (HR, 1.07; 95% CI, 1.13-1.01; P = 0.012). On Kaplan-Meier analysis, the higher LVECV group (≥ 44.03%) had a significantly greater number of primary outcomes than the others (P = 0.010) (C). Conclusion LVECV on CCT may be useful for predicting responders of CRT and prognosis after CRT implantation.ROC curve and Kaplan-Meier analysis

Imaging signs of carotid plaque vulnerability predict subclinical neurological events in asymptomatic patients: the carotid artery multi-modality imaging prognostic study

Abstract Background Carotid artery plaques should be considered for invasive treatment if diameter stenoses is ≥60%, in the presence of clinical and/or imaging characteristics associated with an increased risk of ipsilateral stroke, such as intraplaque haemorrhage (IPH) or lipid-rich necrotic core (LRNC). However, little is known about plaque’s characteristics in patients with &amp;lt;60% stenoses. Purpose To evaluate the prevalence and significance of imaging signs of plaque vulnerability in patients with asymptomatic &amp;lt;60% carotid artery stenoses. Methods In the Carotid Artery Multi-modality imaging Prognostic (CAMP) study (granted by Bando Ricerca Salute 2018 - Regione Toscana) we prospectively enrolled 200 patients with asymptomatic, mild/moderate (40-60%) carotid artery stenoses, as assessed at Doppler ultrasound (DUS). All patients were evaluated with multimodality imaging, including computed tomography angiography (CTA), magnetic resonance angiography (MRA) and brain magnetic resonance imaging (MRI), whenever not contraindicated. A subgroup of 75 patients underwent also a 18[F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). A thorough clinical, biochemical, cardiological and neurological evaluation was performed in all patients. Results Imaging signs of plaque vulnerability were frequent (IPH and/or LRNC at MRA were found in 26.3% patients, plaque ulceration at CTA was found in 36.7% of patients). No difference in the prevalence of cardiovascular risk factors was noted in those with and without signs of vulnerability. Subclinical embolic brain infarctions at brain MRI were found in 8.8% of patients at enrollment. These patients had more frequently a LRNC at MRA than patients without subclinical embolic brain infarctions (50% vs 17%, p&amp;lt;0.05), lower estimated glomerular filtration rate (55±8 vs 73±23 mL/min/1.73mq, p&amp;lt;0.001), higher troponin HS values (16±4 vs 12±8 ng/ml, p&amp;lt;0.05). Presence of LRNC at MRA was the only predictor of embolic lesions at MRI (odds ratio 4.86, 95% confidence interval 1.08-21.8, p&amp;lt;0.05). Conclusions Imaging signs of vulnerability are highly prevalent in patients with asymptomatic intermediate carotid artery stenosis. Presence of a LRNC at MRA is associated with subclinical embolic brain infarcts. The use of non-invasive multi-imaging can better characterize carotid plaques, independent of the degree of stenosis, and help identifying a subgroup of patients at higher risk of events.

ANALYSIS-ASSOCIATED FACTORS INTERFERING WITH DIFFUSION TENSOR INDICES OF PERIPHERAL NERVES

Diffusion tensor imaging (DTI) enables a non-invasive assessment of tissue architecture based on water diffusion. Advancements in technology have expanded the application of DTI from the central nervous system to the peripheral nervous system. High-resolution magnetic resonance imaging (MRI) systems have further enhanced the visualization of nerve compartments. This study investigates the influence of region of interest (ROI) selection on DTI indices in ex vivoperipheral nerves. Cadaveric median nerves (n=10) were harvested and immersed in fluorinated-carbon liquid, and 9-mm segments were independently scanned with a 9.4-T MRI system (scanning time 40 h). Diffusion-weighted signals were summed, and diffusion tensors were calculated for anatomical compartments using different delineation techniques. Following the initial scan, five samples were scanned for the second time using an identical protocol. The analysis showed that the inclusion of an inert background into the ROI significantly reduces fractional anisotropy (FA). Significant differences in diffusion tensors were observed between the initial and intermediate nerve portions, with FA and mean diffusivity (MD) differing by as much as 25.2% and 25.6%, respectively. Tracing the fascicles without the interfascicular epineurium exhibited an 8.8% lower FA compared to the delineations of the epineurium. Second MRI scans showed significant changes in diffusion tensors with higher eigenvalues D1-D3 and MD. In conclusion, the intermediate portions of the nerve demonstrated greater consistency in DTI indices and are therefore recommended for analysis over the initial portions. Using an inert liquid can minimize background effects, but the inherent diffusion properties of the tissue must be carefully considered. Prolonged scanning times can alter diffusion tensors, likely due to autolytic processes, underscoring the importance of consistent pre-scanning conditions and acquisition protocols. Additionally, maintaining consistency in delineations is paramount, regardless of whether the tracing method includes or excludes the interfascicular epineurium.

Arthroscopic Management of Pigmented Villonodular Synovitis of the Hip: A Systematic Review

Background/Objectives: Pigmented villonodular synovitis (PVNS) is a benign proliferation of synovial tissue that can cause joint damage. The hip, although less commonly affected than the knee, presents a challenging diagnosis and treatment, with magnetic resonance imaging (MRI) as the gold standard for detection. Surgical excision, arthroscopic or open, is the main treatment approach, but there is no consensus on the best strategy for the hip. The aim of this systematic review is to evaluate the clinical outcomes, complications, and revision rates associated with arthroscopic hip surgery for PVNS. Methods: A systematic review was performed following the PRISMA guidelines. Relevant studies were identified by searching four databases: PubMed, Scopus, Embase, and Medline. Selected articles were evaluated according to the criteria of levels of evidence (LoE). For retrospective studies, the Coleman Methodology Score (mCMS) was used. This systematic review was registered with the International Prospective Register of Systematic Reviews. Results: Six studies satisfied the criteria; these involved 77 patients (48% male, 52% female) with a mean age of 26.4 years and a mean follow-up of 54.3 months. MRI and biopsy confirmed the diagnoses, and arthroscopic synovectomy was the primary treatment. Success rates ranged from 80% to 100%, with a recurrence rate of 7.8%, 1.3% requiring revision surgery, and eight (10.4%) patients in three studies reporting conversion to THA. Complications included mild effusions and residual synovitis. All patients who underwent a subsequent total hip arthroplasty were affected by advanced osteoarthritis. Conclusions: Our systematic review reveals that the use of hip arthroscopy in diagnosing and treating PVNS has shown satisfactory results without increasing the risk of recurrence or complications and can return patients to their former activity levels, provided their preoperative osteochondral status is good and there is early management of PVNS of the hip joint.

A pipeline for developing digital cardiac twins integrating cardiovascular magnetic resonance and electrocardiographic imaging: results from the MyoFit46 study

Abstract Background Personalised cardiovascular medicine uses multimodal screening and diagnostic tools, spanning from organ to tissue to molecular levels, to generate a complex and detailed patient phenotype. Cardiac digital twins are powerful tools capable of merging and explore these multimodal data by developing virtual, mechanistic and predictive versions of the patient's heart. State-of-the-art pipelines are mainly based on artificial intelligence and optimization process to replicate clinical data and not used it as an input. We present a proof-of-principle pipeline for building digital heart twins based on cardiovascular magnetic resonance (CMR) imaging and integrated electrocardiographic imaging (ECGI) for diverse clinical scenarios by integrating them into the model (Fig. 1). Methods CMR at 3T was performed on participants all born in the same week in March 1946, as part of the longest-running continued surveillance birth cohort: the National Survey of Health and Development. Cine steady-state free precession end-diastolic frames provided anatomical information per participant while CMR multiparametric mapping and late gadolinium enhancement (LGE) provided tissue characteristics to the electrical myocardial model used in the finite element solver Alya. Lastly, the ECGI activation map was used as a source to define the intrinsic endocardial activation sequence by applying a case-specific correction based on wall thickness and myofibers orientation. Activation-repolarization intervals map was used to introduce the personalised repolarization heterogeneities. Results In total, 406 prospectively recruited participants (77.8 ± 0.1 years, 44% male) had multiparametric CMR with ECGI for digital twin reconstruction. The pipeline’s performance was evaluated by measuring the root mean square error (RMSE) between the ECGI activation and repolarization maps with the in-silico ones obtained without applying the proposed pipeline (Baseline) and after its application (ecgi2model). Results obtained using ecgi2model pipeline presented a significantly reduced activation and repolarization RMSE (Fig. 2b), even providing accurate results in patients with different LGE patterns (Fig. 2c). Conclusion Personalised virtual heart models can be constructed at scale using real-world myocardial structural, functional, and electrical properties, from advanced CMR and ECGI data. Proposed digital twins provide a framework for personalised arrhythmic risk assessment based on real clinical data and also its applicability for in-silico clinical trials. Fig.1 Digital twins pipeline. Fig.2 a) Flattened epicardial map. b) RMSE of activation (ACT), repolarization (RPL) and activation-repolarization intervals (ARI) for the different methods methods. c) ACT and RPL maps obtained from ECGI, baseline simulation and ecgi2model simulation in a healthy participant with normal myocardial tissue, another with subendocardial LGE, and another with subepicardial LGE.Figure 1Figure 2

A Novel Mouse Model for Cerebral Inflammatory Demyelination in X-Linked Adrenoleukodystrophy: Insights into Pathogenesis and Potential Therapeutic Targets.

X-linked adrenoleukodystrophy (ALD) is caused by mutations in ABCD1, a peroxisomal gene. More than half of males with an ABCD1 mutation develop inflammatory cerebral demyelination (cALD), but underlying mechanisms remain unknown and therapies are limited. We sought to develop and characterize a mouse model of cALD to facilitate study of disease mechanisms and therapy development. We used immunoassays and immunohistochemistry to assess novel (interleukin 18 [IL-18]) and established molecular markers in cerebrospinal fluid (CSF) and postmortem brain tissue from cALD patients. We generated a cALD phenotype in Abcd1-knockout mice using a 2-hit method that combines cuprizone and experimental autoimmune encephalomyelitis models. We then used magnetic resonance imaging (MRI) and immunohistochemistry to assess the fidelity of cALD molecular markers in the mice. Human and mouse cALD lesions shared histologic features of myelin phagocytosis, myelin loss, abundant microglial activation, T and B-cell infiltration, and astrogliosis. Compared to wild-type controls, Abcd1-knockout mice displayed more cerebral demyelination, blood-brain barrier disruption, and perivascular immune cell infiltration. This enhanced inflammatory response was associated with higher levels of fibrin deposition, oxidative stress, demyelination, and axonal injury. IL-18 immunoreactivity co-localized with perivascular monocytes/macrophages in both human and mouse brain tissue. In cALD patients, CSF IL-18 levels correlated with MRI lesion severity. Our results suggest loss of Abcd1 function in mice predisposes to more severe blood-brain barrier disruption, cerebral inflammation driven by the infiltration of peripheral immune cells, demyelination, and axonal damage, replicating human cALD features. This novel mouse model could shed light on cALD mechanisms and accelerate cALD therapy development. ANN NEUROL 2024.

Integrated multi-omics predictive analysis of atherosclerosis: a sub-study from the Mineralocorticoid Receptor Antagonism in Diabetic Atherosclerosis (MAGMA) trial

Abstract Background/Introduction Mineralocorticoid receptor (MR) antagonists (MRA) are beneficial in cardiorenal outcomes in randomized controlled trials but the mechanisms are unclear. MAGMA was an NHLBI sponsored randomized, double-blind, placebo controlled, 12-month trial comparing Spironolactone (n = 37) vs. placebo (n = 42) in Type 2 diabetics with CKD stages 3-4 on maximal renin-angiotensin system (RAS) blockade and a prior atherosclerotic event and/or left ventricular (LV) hypertrophy. The primary outcome of percent (%) change in total aortic wall volume (TWV) at 12 months, measured by magnetic resonance imaging (MRI), was significantly reduced by Spironolactone. Purpose/Originality The purpose of this analysis was to understand mechanistic pathways of MRAs using a multi-omics approach that could help tease out molecular mechanisms of benefit. Revealing for the first time which of these integrated pathways are predictive of the primary outcome will help design treatments for targeted interventions. Methods Plasma and peripheral blood mononuclear cells from patients randomized to Spironolactone or placebo at baseline and 3-months were measured for aptamer-based proteomic biomarkers (7,596 proteins) and 10-X platform-based single-cell RNA-sequencing (scRNAseq), respectively. Pre-selected candidate predictors were used as inputs of a predictive model of changes of TWV. We fit a Mixed-Multivariate Random Forest (RF) model, a variation of the RF supervised tree-based machine learning method to take the experimental design into account in the regression formulation. The two sources of "omics predictors" were integrated into a supervised multi-omics model to jointly explain the outcome using an extension of Sparse Generalized Canonical Correlation Analysis (SGCCA). Integrated multiome functional analyses with graphical visualizations were carried out by statistical enrichment analysis using Over Representation Analysis (ORA) and Gene Set Enrichment Analysis (GSEA) against databases of gene ontologies, biological pathways, putative regulatory motifs, proteins, or disease annotations. Results The plasma proteome in response to Spironolactone revealed downregulation of MR targets including fibrosis, immune activation/inflammation, leukocyte activation, proliferation and pathways involved in cytokine stimulation. scRNAseq pathways revealed negative regulation of cytokines production such as IL-2 and redistribution of multiple cell types. Predictors of plaque progression involved cytokine-receptor, complement-coagulation, cell adhesion and axonal guidance targets. Multiome integrated functional analyses results of predictive pathways will be presented. Conclusions The changes in plasma proteomic profile with Spironolactone were consistent with the phenotype of reduced atherosclerosis and downregulation of multiple inflammatory, immune response and profibrotic pathways.

Characterization of myocardial ischemia-reperfusion injury in a pig model with novel CW T1r and RAFF2 MRI methods in 1.5T

Abstract Introduction Myocardial ischemia-reperfusion injury (IRI) occurs after myocardial infarction when reperfusion aggravates the initial damage in myocardium by vast infiltration of inflammatory cells and elevated oxidative stress in myocardium that may lead to cardiac remodeling, heart failure and even death [1]. Magnetic resonance imaging (MRI) can accurately determine the anatomy of the heart and to characterize myocardial tissue. Novel endogenous rotating frame MRI methods, including continuous wave (CW) T1r and relaxation along a fictitious field with rank 2 (RAFF2), have been shown to characterize MI and other CVD in mouse and human myocardium with high sensitivity and specificity [2,3]. CW T1r and RAFF2 contrasts are occurring during radio frequency (RF) pulse (in kHz range) making them to be sensitive to slow molecular motions [2]. Comparing to conventional endogenous T1 and T2 methods, these are occurring after the RF pulse (in Larmor frequency (MHz) range) and therefore, these are non-selectively sensitive to different correlation times [4]. Golden standard to image MI is to use contrast agent (CA) in late gadolinium enhancement (LGE) method [2,4]. Using CA has drawbacks and therefore, there is an urgent need for optimizing the endogenous MRI methods in clinical practice. Purpose To characterize myocardial IRI in a pig model and to determine the sensitivity of both novel and conventional cardiac MRI methods. Methods IRI operation was done in 7 pig (30-35 kg) by occluding the LAD with a balloon catheter for 50 minutes. Imaging was done with 1.5T (MAGNETOM Aera) at 3 days and 28 days after the operation. Pig hearts were imaged with conventional native T1, T2, LGE, and with novel CW T1r and RAFF2 methods in both time points. These were imaged before CA injection and LGE was done 25 minutes after CA injection. Relaxation time mappings were done in a pixel-by-pixel manner with monoexponentially fitting. Region-of-interest (ROI) analysis was done to determine the relaxation times in IRI and remote areas. LGE was used to confirm the IRI areas in the myocardium. Relative relaxation time difference (RRTD)-values were calculated with the function of (((Relaxation Time of IRI area) – (Relaxation Time of Remote Area))/ (Relaxation Time of Remote Area)) to determine the contrast difference between IRI and remote areas. Results Relaxation times were elevated in IRI areas compared to remote areas (Figure 1A). Novel rotating frame RRTD-values were significantly higher than RRTD-values in conventional methods. This means that novel methods have larger contrast difference between IRI and remote areas compared to conventional methods, which indicates that novel methods are sensitive to characterize IRI area (Figure 1B). The location of MI areas was similar in both novel rotating frame and conventional methods compared to LGE (Figure 2). Conclusion Novel rotating frame relaxation time methods are sensitive to characterize the IRI area in pig model.Relaxation times, RRTD-valuesRelaxation times maps and LGE