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BACKGROUND: Rapamycin is an inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, and preclinical data demonstrate that it is a promising candidate for a general gero- and neuroprotective treatment in humans. Results from mouse models of Alzheimer's disease have shown beneficial effects of rapamycin, including preventing or reversing cognitive deficits, reducing amyloid oligomers and tauopathies and normalizing synaptic plasticity and cerebral glucose uptake. The "Evaluating Rapamycin Treatment in Alzheimer's Disease using Positron Emission Tomography" (ERAP) trial aims to test if these results translate to humans through evaluating the change in cerebral glucose uptake following six months of rapamycin treatment in participants with early-stage Alzheimer's disease. METHODS: ERAP is a six-month-long, single-arm, open-label, phase IIa biomarker-driven study evaluating if the drug rapamycin can be repurposed to treat Alzheimer's disease. Fifteen patients will be included and treated with a weekly dose of 7 mg rapamycin for six months. The primary endpoint will be change in cerebral glucose uptake, measured using [18F]FDG positron emission tomography. Secondary endpoints include changes in cognitive measures, markers in cerebrospinal fluid as well as cerebral blood flow measured using magnetic resonance imaging. As exploratory outcomes, the study will assess change in multiple age-related pathological processes, such as periodontal inflammation, retinal degeneration, bone mineral density loss, atherosclerosis and decreased cardiac function. DISCUSSION: The ERAP study is a clinical trial using in vivo imaging biomarkers to assess the repurposing of rapamycin for the treatment of Alzheimer's disease. If successful, the study would provide a strong rationale for large-scale evaluation of mTOR-inhibitors as a potential disease-modifying treatment in Alzheimer's disease. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06022068, date of registration 2023-08-30.
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Enfermedad de Alzheimer , Trastornos del Conocimiento , Humanos , Envejecimiento , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/complicaciones , Péptidos beta-Amiloides/líquido cefalorraquídeo , Ensayos Clínicos Fase II como Asunto , Glucosa/metabolismo , Tomografía de Emisión de Positrones/métodos , Serina-Treonina Quinasas TORRESUMEN
BACKGROUND: Decisions in the management of aortic stenosis are based on the peak pressure drop, captured by Doppler echocardiography, whereas gold standard catheterization measurements assess the net pressure drop but are limited by associated risks. The relationship between these two measurements, peak and net pressure drop, is dictated by the pressure recovery along the ascending aorta which is mainly caused by turbulence energy dissipation. Currently, pressure recovery is considered to occur within the first 40-50 mm distally from the aortic valve, albeit there is inconsistency across interventionist centers on where/how to position the catheter to capture the net pressure drop. METHODS: We developed a non-invasive method to assess the pressure recovery distance based on blood flow momentum via 4D Flow cardiovascular magnetic resonance (CMR). Multi-center acquisitions included physical flow phantoms with different stenotic valve configurations to validate this method, first against reference measurements and then against turbulent energy dissipation (respectively n = 8 and n = 28 acquisitions) and to investigate the relationship between peak and net pressure drops. Finally, we explored the potential errors of cardiac catheterisation pressure recordings as a result of neglecting the pressure recovery distance in a clinical bicuspid aortic valve (BAV) cohort of n = 32 patients. RESULTS: In-vitro assessment of pressure recovery distance based on flow momentum achieved an average error of 1.8 ± 8.4 mm when compared to reference pressure sensors in the first phantom workbench. The momentum pressure recovery distance and the turbulent energy dissipation distance showed no statistical difference (mean difference of 2.8 ± 5.4 mm, R2 = 0.93) in the second phantom workbench. A linear correlation was observed between peak and net pressure drops, however, with strong dependences on the valvular morphology. Finally, in the BAV cohort the pressure recovery distance was 78.8 ± 34.3 mm from vena contracta, which is significantly longer than currently accepted in clinical practise (40-50 mm), and 37.5% of patients displayed a pressure recovery distance beyond the end of the ascending aorta. CONCLUSION: The non-invasive assessment of the distance to pressure recovery is possible by tracking momentum via 4D Flow CMR. Recovery is not always complete at the ascending aorta, and catheterised recordings will overestimate the net pressure drop in those situations. There is a need to re-evaluate the methods that characterise the haemodynamic burden caused by aortic stenosis as currently clinically accepted pressure recovery distance is an underestimation.
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Estenosis de la Válvula Aórtica , Enfermedad de la Válvula Aórtica Bicúspide , Humanos , Valor Predictivo de las Pruebas , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Válvula Aórtica/diagnóstico por imagen , Hemodinámica , Espectroscopía de Resonancia Magnética , Velocidad del Flujo Sanguíneo/fisiologíaRESUMEN
PURPOSE: Hemodynamic alterations are indicative of cerebrovascular disease. However, the narrow and tortuous cerebrovasculature complicates image-based assessment, especially when quantifying relative pressure. Here, we present a systematic evaluation of image-based cerebrovascular relative pressure mapping, investigating the accuracy of the routinely used reduced Bernoulli (RB), the extended unsteady Bernoulli (UB), and the full-field virtual work-energy relative pressure ( ν WERP) method. METHODS: Patient-specific in silico models were used to generate synthetic cerebrovascular 4D Flow MRI, with RB, UB, and ν WERP performance quantified as a function of spatiotemporal sampling and image noise. Cerebrovascular relative pressures were also derived in 4D Flow MRI from healthy volunteers ( n=8 ), acquired at two spatial resolutions (dx = 1.1 and 0.8 mm). RESULTS: The in silico analysis indicate that accurate relative pressure estimations are inherently coupled to spatial sampling: at dx = 1.0 mm high errors are reported for all methods; at dx = 0.5 mm ν WERP recovers relative pressures at a mean error of 0.02 ± 0.25 mm Hg, while errors remain higher for RB and UB (mean error of -2.18 ± 1.91 and -2.18 ± 1.87 mm Hg, respectively). The dependence on spatial sampling is also indicated in vivo, albeit with higher correlative dependence between resolutions using ν WERP (k = 0.64, R2 = 0.81 for dx = 1.1 vs. 0.8 mm) than with RB or UB (k = 0.04, R2 = 0.03, and k = 0.07, R2 = 0.07, respectively). CONCLUSION: Image-based full-field methods such as ν WERP enable cerebrovascular relative pressure mapping; however, accuracy is directly dependent on utilized spatial resolution.
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Imagenología Tridimensional , Imagen por Resonancia Magnética , Velocidad del Flujo Sanguíneo , Simulación por Computador , Voluntarios Sanos , Hemodinámica , HumanosRESUMEN
BACKGROUND: Chronic type B aortic dissection (TBAD) is associated with poor long-term outcome, and accurate risk stratification tools remain lacking. Pressurization of the false lumen (FL) has been recognized as central in promoting aortic growth. Several surrogate imaging-based metrics have been proposed to assess FL hemodynamics; however, their relationship to enlarging aortic dimensions remains unclear. We investigated the association between aortic growth and three cardiovascular magnetic resonance (CMR)-derived metrics of FL pressurization: false lumen ejection fraction (FLEF), maximum systolic deceleration rate (MSDR), and FL relative pressure (FL ΔPmax). METHODS: CMR/CMR angiography was performed in 12 patients with chronic dissection of the descending thoracoabdominal aorta, including contrast-enhanced CMR angiography and time-resolved three-dimensional phase-contrast CMR (4D Flow CMR). Aortic growth rate was calculated as the change in maximal aortic diameter between baseline and follow-up imaging studies over the time interval, with patients categorized as having either 'stable' (< 3 mm/year) or 'enlarging' (≥ 3 mm/year) growth. Three metrics relating to FL pressurization were defined as: (1) FLEF: the ratio between retrograde and antegrade flow at the TBAD entry tear, (2) MSDR: the absolute difference between maximum and minimum systolic acceleration in the proximal FL, and (3) FL ΔPmax: the difference in absolute pressure between aortic root and distal FL. RESULTS: FLEF was higher in enlarging TBAD (49.0 ± 17.9% vs. 10.0 ± 11.9%, p = 0.002), whereas FL ΔPmax was lower (32.2 ± 10.8 vs. 57.2 ± 12.5 mmHg/m, p = 0.017). MSDR and conventional anatomic variables did not differ significantly between groups. FLEF showed positive (r = 0.78, p = 0.003) correlation with aortic growth rate whereas FL ΔPmax showed negative correlation (r = - 0.64, p = 0.026). FLEF and FL ΔPmax remained as independent predictors of aortic growth rate after adjusting for baseline aortic diameter. CONCLUSION: Comparative analysis of three 4D flow CMR metrics of TBAD FL pressurization demonstrated that those that focusing on retrograde flow (FLEF) and relative pressure (FL ΔPmax) independently correlated with growth and differentiated patients with enlarging and stable descending aortic dissections. These results emphasize the highly variable nature of aortic hemodynamics in TBAD patients, and suggest that 4D Flow CMR derived metrics of FL pressurization may be useful to separate patients at highest and lowest risk for progressive aortic growth and complications.
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Aneurisma de la Aorta Torácica , Disección Aórtica , Disección Aórtica/diagnóstico por imagen , Aorta , Hemodinámica , Humanos , Espectroscopía de Resonancia Magnética , Valor Predictivo de las Pruebas , Resultado del TratamientoRESUMEN
This retrospective cohort study aimed to assess whether basal septal wall thickness (BSWT), anterior (AML) and posterior (PML) mitral leaflet length, or sex were associated with remaining left ventricular outflow tract obstruction (LVOTO) in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing alcohol septal ablation (ASA). One hundred fifty-four patients who underwent ASA at the Karolinska University Hospital in Stockholm, Sweden, between 2009 and 2021, were included retrospectively. Anatomical and hemodynamic parameters were collected from invasive catheterization before and during ASA, and from echocardiography (ECHO) examinations before, during, and at 1-year follow-up after ASA. Linear and logistic regression models were used to assess the association between sex, BSWT, AML, PML, and outcome, which was defined as the remaining LVOTO (≥ 30 mmHg) after ASA. The median follow-up was 364 days (interquartile range 334-385 days). BSWT ≥ 23 mm (n = 13, 12%) was associated with remaining LVOTO at follow-up (p = 0.004). Elongated mitral valve leaflet length (either AML or PML) was present in 125 (90%) patients. Elongated AML (> 24 mm) was present in 67 (44%) patients, although AML length was not associated with remaining LVOTO at follow-up. Elongated PML (> 14 mm) was present in 114 (74%) patients and was not associated with remaining LVOTO at follow-up. No significant sex differences were observed regarding the remaining LVOTO. ECHO measurement of BSWT can be effectively used to select patients for successful ASA and identify those patients with a risk of incomplete resolution of LVOTO after ASA.
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4D Flow Magnetic Resonance Imaging (4D Flow MRI) is a non-invasive measurement technique capable of quantifying blood flow across the cardiovascular system. While practical use is limited by spatial resolution and image noise, incorporation of trained super-resolution (SR) networks has potential to enhance image quality post-scan. However, these efforts have predominantly been restricted to narrowly defined cardiovascular domains, with limited exploration of how SR performance extends across the cardiovascular system; a task aggravated by contrasting hemodynamic conditions apparent across the cardiovasculature. The aim of our study was therefore to explore the generalizability of SR 4D Flow MRI using a combination of existing super-resolution base models, novel heterogeneous training sets, and dedicated ensemble learning techniques; the latter-most being effectively used for improved domain adaption in other domains or modalities, however, with no previous exploration in the setting of 4D Flow MRI. With synthetic training data generated across three disparate domains (cardiac, aortic, cerebrovascular), varying convolutional base and ensemble learners were evaluated as a function of domain and architecture, quantifying performance on both in-silico and acquired in-vivo data from the same three domains. Results show that both bagging and stacking ensembling enhance SR performance across domains, accurately predicting high-resolution velocities from low-resolution input data in-silico. Likewise, optimized networks successfully recover native resolution velocities from downsampled in-vivo data, as well as show qualitative potential in generating denoised SR-images from clinicallevel input data. In conclusion, our work presents a viable approach for generalized SR 4D Flow MRI, with the novel use of ensemble learning in the setting of advanced fullfield flow imaging extending utility across various clinical areas of interest.
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OBJECTIVE: Guidance for preventing myocardial infarction and ischemic stroke by tailoring treatment for individual patients with atherosclerosis is an unmet need. Such development may be possible with computational modeling. Given the multifactorial biology of atherosclerosis, modeling must be based on complete biological networks that capture protein-protein interactions estimated to drive disease progression. Here, we aimed to develop a clinically relevant scale model of atherosclerosis, calibrate it with individual patient data, and use it to simulate optimized pharmacotherapy for individual patients. APPROACH AND RESULTS: The study used a uniquely constituted plaque proteomic dataset to create a comprehensive systems biology disease model for simulating individualized responses to pharmacotherapy. Plaque tissue was collected from 18 patients with 6735 proteins at two locations per patient. 113 pathways were identified and included in the systems biology model of endothelial cells, vascular smooth muscle cells, macrophages, lymphocytes, and the integrated intima, altogether spanning 4411 proteins, demonstrating a range of 39-96% plaque instability. After calibrating the systems biology models for individual patients, we simulated intensive lipid-lowering, anti-inflammatory, and anti-diabetic drugs. We also simulated a combination therapy. Drug response was evaluated as the degree of change in plaque stability, where an improvement was defined as a reduction of plaque instability. In patients with initially unstable lesions, simulated responses varied from high (20%, on combination therapy) to marginal improvement, whereas patients with initially stable plaques showed generally less improvement. CONCLUSION: In this pilot study, proteomics-based system biology modeling was shown to simulate drug response based on atherosclerotic plaque instability with a power of 90%, providing a potential strategy for improved personalized management of patients with cardiovascular disease.
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Aterosclerosis , Enfermedades Cardiovasculares , Placa Aterosclerótica , Humanos , Enfermedades Cardiovasculares/tratamiento farmacológico , Proteómica , Medicina de Precisión , Células Endoteliales/metabolismo , Células Endoteliales/patología , Calibración , Proyectos Piloto , Aterosclerosis/tratamiento farmacológico , Simulación por ComputadorRESUMEN
Changes in cardiovascular hemodynamics are closely related to the development of aortic regurgitation (AR), a type of valvular heart disease. Metrics derived from blood flows are used to indicate AR onset and evaluate its severity. These metrics can be non-invasively obtained using four-dimensional (4D) flow magnetic resonance imaging (MRI), where accuracy is primarily dependent on spatial resolution. However, insufficient resolution often results from limitations in 4D flow MRI and complex aortic regurgitation hemodynamics. To address this, computational fluid dynamics simulations were transformed into synthetic 4D flow MRI data and used to train a variety of neural networks. These networks generated super-resolution, full-field phase images with an upsample factor of 4. Results showed decreased velocity error, high structural similarity scores, and improved learning capabilities from previous work. Further validation was performed on two sets of in vivo 4D flow MRI data and demonstrated success in de-noising flow images. This approach presents an opportunity to comprehensively analyse AR hemodynamics in a non-invasive manner.
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Insuficiencia de la Válvula Aórtica , Aprendizaje Profundo , Humanos , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Velocidad del Flujo Sanguíneo/fisiología , Hidrodinámica , Valor Predictivo de las Pruebas , Imagen por Resonancia Magnética/métodos , Hemodinámica , Imagenología Tridimensional/métodosRESUMEN
Aims: Non-invasive estimation of mean pulmonary artery pressure (mPAP) by cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow analysis has shown excellent agreement with invasive right heart catheterization. However, clinical application is limited by relatively long scan times. Therefore, the aim of this study was to evaluate the accuracy and time reduction of compressed sensing (CS) accelerated acquisition for mPAP estimation. Methods and results: Patients (n = 51) referred for clinical CMR at 1.5â T or 3â T underwent imaging with both a prototype CS-accelerated and a non-CS-accelerated flow sequence acquiring time-resolved multiple 2D slice phase-contrast three-directional velocity-encoded images covering the pulmonary artery. Prototype software was used for the blinded analysis of pulmonary artery (PA) vortex duration to estimate mPAP as previously validated. CS-accelerated and non-CS-accelerated acquisition showed increased mPAP in 22/51 (43%) and 24/51 (47%) patients, respectively. The mean bias for estimating mPAP between the two methods was 0.1 ± 1.9â mmHg and the intraclass correlation coefficient was 0.97 (95% confidence interval 0.94-0.98). Effective scan time was lower for the CS-accelerated acquisition (1â min 55â s ± 27â s vs. 9â min 6â s ± 2â min 20â s, P < 0.001, 79% reduction). Conclusions: CS-accelerated CMR acquisition enables preserved accuracy for estimating mPAP compared to a non-CS-accelerated sequence, allowing for an average scan time of less than 2â min. CS-acceleration thereby increases the clinical utility of CMR 4D flow analysis to estimate mPAP.
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4D Flow Magnetic Resonance Imaging (4D Flow MRI) is a non-invasive measurement technique capable of quantifying blood flow across the cardiovascular system. While practical use is limited by spatial resolution and image noise, incorporation of trained super-resolution (SR) networks has potential to enhance image quality post-scan. However, these efforts have predominantly been restricted to narrowly defined cardiovascular domains, with limited exploration of how SR performance extends across the cardiovascular system; a task aggravated by contrasting hemodynamic conditions apparent across the cardiovasculature. The aim of our study was to explore the generalizability of SR 4D Flow MRI using a combination of heterogeneous training sets and dedicated ensemble learning. With synthetic training data generated across three disparate domains (cardiac, aortic, cerebrovascular), varying convolutional base and ensemble learners were evaluated as a function of domain and architecture, quantifying performance on both in-silico and acquired in-vivo data from the same three domains. Results show that both bagging and stacking ensembling enhance SR performance across domains, accurately predicting high-resolution velocities from low-resolution input data in-silico. Likewise, optimized networks successfully recover native resolution velocities from downsampled in-vivo data, as well as show qualitative potential in generating denoised SR-images from clinicallevel input data. In conclusion, our work presents a viable approach for generalized SR 4D Flow MRI, with ensemble learning extending utility across various clinical areas of interest.
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BACKGROUND: Intraplaque hemorrhage (IPH) is a hallmark of atherosclerotic plaque instability. Biliverdin reductase B (BLVRB) is enriched in plasma and plaques from patients with symptomatic carotid atherosclerosis and functionally associated with IPH. OBJECTIVE: We explored the biomarker potential of plasma BLVRB through (1) its correlation with IPH in carotid plaques assessed by magnetic resonance imaging (MRI), and with recurrent ischemic stroke, and (2) its use for monitoring pharmacotherapy targeting IPH in a preclinical setting. METHODS: Plasma BLVRB levels were measured in patients with symptomatic carotid atherosclerosis from the PARISK study (n = 177, 5 year follow-up) with and without IPH as indicated by MRI. Plasma BLVRB levels were also measured in a mouse vein graft model of IPH at baseline and following antiangiogenic therapy targeting vascular endothelial growth factor receptor 2 (VEGFR-2). RESULTS: Plasma BLVRB levels were significantly higher in patients with IPH (737.32 ± 693.21 vs. 520.94 ± 499.43 mean fluorescent intensity (MFI), p = 0.033), but had no association with baseline clinical and biological parameters. Plasma BLVRB levels were also significantly higher in patients who developed recurrent ischemic stroke (1099.34 ± 928.49 vs. 582.07 ± 545.34 MFI, HR = 1.600, CI [1.092-2.344]; p = 0.016). Plasma BLVRB levels were significantly reduced following prevention of IPH by anti-VEGFR-2 therapy in mouse vein grafts (1189 ± 258.73 vs. 1752 ± 366.84 MFI; p = 0.004). CONCLUSIONS: Plasma BLVRB was associated with IPH and increased risk of recurrent ischemic stroke in patients with symptomatic low- to moderate-grade carotid stenosis, indicating the capacity to monitor the efficacy of IPH-preventive pharmacotherapy in an animal model. Together, these results suggest the utility of plasma BLVRB as a biomarker for atherosclerotic plaque instability.
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Enfermedades de las Arterias Carótidas , Accidente Cerebrovascular Isquémico , Placa Aterosclerótica , Animales , Humanos , Ratones , Biomarcadores/sangre , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/complicaciones , Hemorragia/sangre , Hemorragia/diagnóstico por imagen , Hemorragia/etiología , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/etiología , Placa Aterosclerótica/sangre , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/patología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
Shear wave elastography (SWE) is a promising technique for characterizing carotid plaques and assessing local arterial stiffness. The mechanical stress to which the tissue is subjected during SWE using acoustic radiation force (ARF), leading to strain at a certain strain rate, is still relatively unknown. Because SWE is increasingly used for arterial applications where the mechanical stress could potentially lead to significant consequences, it is important to understand the risks of SWE-induced strain and strain rate. The aim of this study was to investigate the safety of SWE in terms of induced arterial strain and strain rateex-vivoand in a human carotid arteryin-vivo. SWE was performed on six porcine aortae as a model of the human carotid artery using different combinations of ARF push parameters (push voltage: 60/90 V, aperture width: f/1.0/1.5, push length: 100/150/200µs) and distance to push position. The largest induced strain and strain rate were 1.46% and 54 s-1(90 V, f/1.0, 200µs), respectively. Moreover, the SWE-induced strains and strain rates increased with increasing push voltage, aperture, push length, and decreasing distance between the region of interest and the push. In the human carotid artery, the SWE-induced maximum strain was 0.06% and the maximum strain rate was 1.58 s-1, compared with the maximum absolute strain and strain rate of 12.61% and 5.12 s-1, respectively, induced by blood pressure variations in the cardiac cycle. Our results indicate thatex-vivoarterial SWE does not expose the artery to higher strain rate than normal blood pressure variations, and to strain one order of magnitude higher than normal blood pressure variations, at the push settings and distances from the region of interest used in this study.
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Diagnóstico por Imagen de Elasticidad , Animales , Aorta/diagnóstico por imagen , Diagnóstico por Imagen de Elasticidad/métodos , Corazón , Humanos , Estrés Mecánico , PorcinosRESUMEN
Atherosclerosis is a complex disease altering vasculature morphology, and subsequently flow, with progressive plaque formation, mural disruption, and lumen occlusion. Determination of clinically-relevant plaque components-particularly calcium, lipid, and fibrous tissue-has driven automated image-based tissue characterization. Atherosclerotic tissue of mixed composition type arises when these principal components interdigitate and combine during the course of progressive atherosclerosis. Nevertheless, such mixed plaque is treated non-uniformly, and often neglected, as a distinct class in image analysis. We therefore quantitatively investigate frameworks to characterize mixed and other plaque tissue types, and examine their implications. Convolutional neural networks operated on labeled intravascular optical coherence tomography images using various characterization frameworks. The treatment of mixed plaque by image-based classifiers influenced the accuracy and homogeneity of the segmented classes. Excluding mixed plaque as a class on to itself necessarily assigns heterogeneous lesion subcomponents to one of the three homogeneous subtypes; when included, 61.7% of mixed tissue is labeled as calcium, reducing specificity in homogeneous calcium detection by 34.8%. Segmenting mixed plaque as distinct from homogeneous, non-mixed tissue improves lesion classification. This can be achieved either on the basis of homogeneous tissue classifier prediction uncertainty (77.8% overall accuracy) or by training classifiers to identify mixed plaque as a discrete tissue class (82.9% overall accuracy). Alternatively, mixed plaque can be grouped with one of the homogeneous classes, yielding a single histologically diverse class that helps preserve the homogeneity of the others. Ultimately, the best approach depends upon the alignment of histological and functional distinctions. While no vascular lesion characterization framework or method is universally optimal or appropriate, context should remain central in selecting tissue characterization techniques.
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Aterosclerosis , Placa Aterosclerótica , Aterosclerosis/diagnóstico por imagen , Calcio , Humanos , Procesamiento de Imagen Asistido por Computador , Placa Aterosclerótica/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodosRESUMEN
Purpose: Modern medical imaging enables clinicians to effectively diagnose, monitor, and treat diseases. However, clinical decision-making often relies on combined evaluation of either longitudinal or disparate image sets, necessitating coregistration of multiple acquisitions. Promising coregistration techniques have been proposed; however, available methods predominantly rely on time-consuming manual alignments or nontrivial feature extraction with limited clinical applicability. Addressing these issues, we present a fully automated, robust, nonrigid registration method, allowing for coregistering of multimodal tomographic vascular image datasets using luminal annotation as the sole alignment feature. Approach: Registration is carried out by the use of the registration metrics defined exclusively for lumens shapes. The framework is primarily broken down into two sequential parts: longitudinal and rotational registration. Both techniques are inherently nonrigid in nature to compensate for motion and acquisition artifacts in tomographic images. Results: Performance was evaluated across multimodal intravascular datasets, as well as in longitudinal cases assessing pre-/postinterventional coronary images. Low registration error in both datasets highlights method utility, with longitudinal registration errors-evaluated throughout the paired tomographic sequences-of 0.29 ± 0.14 mm ( < 2 longitudinal image frames) and 0.18 ± 0.16 mm ( < 1 frame) for multimodal and interventional datasets, respectively. Angular registration for the interventional dataset rendered errors of 7.7 ° ± 6.7 ° , and 29.1 ° ± 23.2 ° for the multimodal set. Conclusions: Satisfactory results across datasets, along with additional attributes such as the ability to avoid longitudinal over-fitting and correct nonlinear catheter rotation during nonrigid rotational registration, highlight the potential wide-ranging applicability of our presented coregistration method.
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Ventricular-vascular interaction is central in the adaptation to cardiovascular disease. However, cardiomyopathy patients are predominantly monitored using cardiac biomarkers. The aim of this study is therefore to explore aortic function in dilated cardiomyopathy (DCM). Fourteen idiopathic DCM patients and 16 controls underwent cardiac magnetic resonance imaging, with aortic relative pressure derived using physics-based image processing and a virtual cohort utilized to assess the impact of cardiovascular properties on aortic behaviour. Subjects with reduced left ventricular systolic function had significantly reduced aortic relative pressure, increased aortic stiffness, and significantly delayed time-to-pressure peak duration. From the virtual cohort, aortic stiffness and aortic volumetric size were identified as key determinants of aortic relative pressure. As such, this study shows how advanced flow imaging and aortic hemodynamic evaluation could provide novel insights into the manifestation of DCM, with signs of both altered aortic structure and function derived in DCM using our proposed imaging protocol.
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Cardiomiopatía Dilatada , Humanos , Hemodinámica , Aorta/diagnóstico por imagen , Ventrículos Cardíacos , Imagen por Resonancia Magnética/métodos , Función Ventricular IzquierdaRESUMEN
The aim of this study was to determine whether specific three-dimensional aortic shape features, extracted via statistical shape analysis (SSA), correlate with the development of thoracic ascending aortic dissection (TAAD) risk and associated aortic hemodynamics. Thirty-one patients followed prospectively with ascending thoracic aortic aneurysm (ATAA), who either did (12 patients) or did not (19 patients) develop TAAD, were included in the study, with aortic arch geometries extracted from computed tomographic angiography (CTA) imaging. Arch geometries were analyzed with SSA, and unsupervised and supervised (linked to dissection outcome) shape features were extracted with principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), respectively. We determined PLS-DA to be effective at separating dissection and no-dissection patients ([Formula: see text]), with decreased tortuosity and more equal ascending and descending aortic diameters associated with higher dissection risk. In contrast, neither PCA nor traditional morphometric parameters (maximum diameter, tortuosity, or arch volume) were effective at separating dissection and no-dissection patients. The arch shapes associated with higher dissection probability were supported with hemodynamic insight. Computational fluid dynamics (CFD) simulations revealed a correlation between the PLS-DA shape features and wall shear stress (WSS), with higher maximum WSS in the ascending aorta associated with increased risk of dissection occurrence. Our work highlights the potential importance of incorporating higher dimensional geometric assessment of aortic arch anatomy in TAAD risk assessment, and in considering the interdependent influences of arch shape and hemodynamics as mechanistic contributors to TAAD occurrence.
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Disección Aórtica , Humanos , Disección Aórtica/diagnóstico por imagen , Aorta , Aorta Torácica/diagnóstico por imagen , HemodinámicaRESUMEN
Aortic surgeries in congenital conditions, such as hypoplastic left heart syndrome (HLHS), aim to restore and maintain the conduit and reservoir functions of the aorta. We proposed a method to assess these two functions based on 4D flow MRI, and we applied it to study the aorta in pre-Fontan HLHS. Ten pre-Fontan HLHS patients and six age-matched controls were studied to derive the advective pressure difference and viscous dissipation for conduit function, and pulse wave velocity and elastic modulus for reservoir function. The reconstructed neo-aorta in HLHS subjects achieved a good conduit function at a cost of an impaired reservoir function (69.7% increase of elastic modulus). The native descending HLHS aorta displayed enhanced reservoir (elastic modulus being 18.4% smaller) but impaired conduit function (three-fold increase in peak advection). A non-invasive and comprehensive assessment of aortic conduit and reservoir functions is feasible and has potentially clinical relevance in congenital vascular conditions.
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Aorta Torácica , Síndrome del Corazón Izquierdo Hipoplásico , Humanos , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Análisis de la Onda del Pulso , Síndrome del Corazón Izquierdo Hipoplásico/cirugía , Aorta/diagnóstico por imagen , Aorta/cirugíaRESUMEN
Drug delivery is central to modern cardiovascular care, where drug-eluting stents, bioresorbable scaffolds, and drug-coated balloons all aim to restore perfusion while inhibiting exuberant healing. The promise and enthusiasm of these devices has in some cases exceeded demonstration of efficacy and even understanding of driving mechanisms. The authors review the means of drug delivery in each device, outlining how the technologies affect vascular behavior. They focus on how drug retention and response are governed by lesion morphology: lipid displacing drug-specific binding sites, calcium inhibiting diffusion, blocking thrombi or promoting luminal washout, and vascular healing steering hyperplastic developments. In this regard, the authors outline the fundamental impact of vascular structure on drug delivery and review the development of contemporary and future devices for coronary and peripheral intervention. They look toward a future where incorporating information on lesion distribution is central to therapeutic success and envision a transition toward lesion-specific treatment for improved interventional outcomes.
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Fármacos Cardiovasculares/farmacología , Stents Liberadores de Fármacos , Enfermedad Arterial Periférica/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Implantes Absorbibles , Sistemas de Liberación de Medicamentos , Humanos , Diseño de PrótesisRESUMEN
The pathophysiology of atherosclerotic lesions, including plaque rupture triggered by mechanical failure of the vessel wall, depends directly on the plaque morphology-modulated mechanical response. The complex interplay between lesion morphology and structural behaviour can be studied with high-fidelity computational modelling. However, construction of three-dimensional (3D) and heterogeneous models is challenging, with most previous work focusing on two-dimensional geometries or on single-material lesion compositions. Addressing these limitations, we here present a semi-automatic computational platform, leveraging clinical optical coherence tomography images to effectively reconstruct a 3D patient-specific multi-material model of atherosclerotic plaques, for which the mechanical response is obtained by structural finite-element simulations. To demonstrate the importance of including multi-material plaque components when recovering the mechanical response, a computational case study was conducted in which systematic variation of the intraplaque lipid and calcium was performed. The study demonstrated that the inclusion of various tissue components greatly affected the lesion mechanical response, illustrating the importance of multi-material formulations. This platform accordingly provides a viable foundation for studying how plaque micro-morphology affects plaque mechanical response, allowing for patient-specific assessments and extension into clinically relevant patient cohorts.