Evaluation Of Arteriovenous Malformations Research Articles

High‐depth next‐generation sequencing panel testing in the evaluation of arteriovenous malformations

Arteriovenous malformations (AVMs) are vascular lesions in which an overgrowth of blood vessels of varying sizes develops with one or more direct connections between the arterial and venous circulation. We performed a retrospective review of a cohort of 54 patients with AVMs referred to our clinical genomic laboratory for high-depth next-generation sequencing (NGS) panel of Disorders of Somatic Mosaicism (DoSM). Thirty-seven of 54 patients were female (68.5%). Among the 54 cases, 37 (68.5%) cases had pathogenic and/or likely pathogenic (P/LP) variants identified, two cases (3.7%) had variants of uncertain clinical significance, and the remaining 15 cases (27.8%) had negative results. MAP2K1 variants were found in 12 cases, followed by eight cases with KRAS variants and seven with TEK variants, and the remainder being identified in several other genes on the panel. Among the 37 positive cases, 32 cases had somatic alterations only; the remaining five cases had at least one germline P/LP variant, including four cases with PTEN and one with RASA1. Of note, two cases had the unexpected co-existence of two P/LP variants. In summary, this study illustrated the molecular diagnostic yield (68.5%) of this cohort of patients with a clinical indication of AVMs by our high-depth DoSM NGS panel.

Clinical Utility of Next-Generation Sequencing Panel Testing in the Evaluation of Arteriovenous Malformations

Abstract Arteriovenous malformations (AVMs) are vascular lesions in which an overgrowth of blood vessels of varying sizes develops with one or more direct connections between the arterial and venous circulation. AVMs are seen in sporadic and syndromic conditions that are caused by a variety of genomic alterations. Here, we performed a retrospective review of the cases sent for next-generation sequencing (NGS) analysis for diseases of somatic mosaicism (DoSM). Specimens from 54 patients with clinical indication of AVMs were submitted for the DoSM NGS panel between October 2013 and Dec 2021. DNA extraction and sequence analysis were performed on affected tissues, including fresh tissue, formalin-fixed paraffin-embedded tissue, fibroblast cultures, and buccal specimens. Single-nucleotide variants (SNVs) with variant allele fractions (VAFs) greater than 3% and small insertions and deletions (indels, <21 bp) were called using VarScan2, Genome Analysis Toolkit (GATK), and Pindel. Variants with VAFs between 1-3% were manually reviewed based on the sequencing data quality and the known clinical significance. 38/54 (69.1%) patients were females and 16/54 (30.9%) were males. Ages ranged from 1 month to 73 years (median age 17 years). Most of the patients were indicated with sporadic AVM (81%), although additional clinical indications were noticed, including unspecified congenital vascular malformation (9.1%), capillary malformation (5.5%), arteriovenous fistula, and AVM associated with capillary and lymphatic malformations (1.8% each). The biopsied lesion was most often located in the head (43.6%), followed by the limbs (30.9%), and unspecified areas of the body in the remaining 25.5%. Among the 54 cases, 37 (68.5%) cases had pathogenic and/or likely pathogenic (P/LP) variants identified, 2 cases (3.7%) had variants of unknown significance, and the remaining 15 cases (27.8%) had negative results. MAP2K1 variants were found in 12 samples, followed by KRAS (8), TEK (7), PTEN (5), BRAF (4), TSC2 (2), HRAS (2), RASA1 (2), and PDGFRB (1). Of note, four cases had two P/LP variants. Among the 37 positive cases, 32 cases had somatic alterations; the remaining 5 cases had at least one germline P/LP variant, including PTEN (4) and RASA1 (1). In summary, the diagnostic yield of cases with clinical indication of AVMs was 68.5% using our in-house DoSM NGS panel. This study demonstrates the clinical utility of the DoSM NGS panel testing in the evaluation of a cohort with clinical presentations of AVMs.

Abstract 122: Transit Time on Digital Subtraction Angiography Correlates with Cerebral Arteriovenous Malformation Flow Measured by Quantitative Magnetic Resonance Angiography

Introduction: Digital subtraction angiography (DSA) currently provides angioarchitectural features of cerebral arteriovenous malformations (AVMs) but its role in the hemodynamic evaluation of AVMs is poorly understood. Here, we assess transit time (TT) of contrast on DSA relative to AVM flow measured using quantitative magnetic resonance angiography (QMRA). Methods: Patients seen at our institution between 2007 and 2014 with a cerebral AVM and DSA and QMRA obtained prior to any treatment were retrospectively reviewed. TT on DSA was defined as time needed for contrast to change image intensity from 10%-100%, 100%-10%, and 25%-25%. TT was correlated to AVM total flow and angio-architectural features. Results: 33 patients (mean age 34.8 years) were included. 7 patients presented with hemorrhage. Mean AVM volume was 13.61 mL (range 0.28-84.2 mL). Higher total flow significantly correlated with shorter TT100%-10% and TT25%-25% (P=0.04, P=0.03, respectively). Total flow was also significantly related to the ratio sum of draining vein diameters/TT (TT10%-100% P=0.04, TT100%-10% P=0.01, TT25%-25% P=0.02). Presence of venous stenosis (P=0.01) and arterial ectasia (P=0.03) correlated significantly with TT100%-10%. TT was not significantly related to hemorrhagic presentation, deep drainage, single draining vein, or Spetzler-Martin grade. Conclusions: TT and the ratio sum of draining vein diameters/TT correlated significantly with AVM total flow measured using QMRA, and so TT along with venous diameters determined from DSA may be used as a surrogate for AVM flow.

Finding the Nidus: Detection and Workup of Non-Central Nervous System Arteriovenous Malformations.

Vascular anomalies are a diverse group of pathologic conditions. They have different manifestations, natural histories, and treatments. Compared with other vascular malformations, arteriovenous malformations (AVMs) are considered the most symptomatic and difficult to manage. AVMs inherently progress and have a high rate of recurrence after treatment. Imaging helps provide an accurate and early diagnosis, which can then be used to direct appropriate management, with embolization evolving as the primary therapy. Thus, radiology plays a crucial role in the detection, workup, and management of AVMs. Ultrasonography (US) is a useful initial imaging modality, particularly when AVMs involve the extremities or a superficial or accessible location. Limitations include poor identification of soft-tissue and bone components, as well as suboptimal evaluation of deep or complex AVMs. Magnetic resonance (MR) angiography is the preferred imaging modality for AVMs and should be considered in any symptomatic patient or in the initial evaluation of vascular anomalies that are equivocal at US. Computed tomographic angiography should be reserved for those patients who are unable to undergo MR angiography or for evaluation of acute symptoms, such as bleeding or airway compromise. Conventional catheter-based angiography is useful for real-time depiction and evaluation of AVMs, particularly in the planning and execution of endovascular treatment and in the diagnosis of an AVM when findings from noninvasive imaging are equivocal for a high-flow component. As with the diagnostic workup, MR angiography is the preferred posttreatment modality. (©)RSNA, 2016.

High-resolution dynamic angiography using flat-panel volume CT: feasibility demonstration for neuro and lower limb vascular applications.

This paper evaluates a prototype flat-panel volume CT (fpVCT) for dynamic in vivo imaging in a variety of neurovascular and lower limb applications. Dynamic CTA was performed on 12 patients (neuro = 8, lower limb = 4) using an fpVCT with 120 kVp, 50 mA, rotation time varying from 8 to 19 s, and field of view of 25 × 25 × 18 cm(3). Four-dimensional data sets (i.e. 3D images over time) were reconstructed and reviewed. Dynamic CTA demonstrated sufficient spatio-temporal resolution to elucidate first-pass and recirculation dynamics of contrast bolus through neurovasclaur pathologies and phasic blood flow though lower-limb vasculature and grafts. The high spatial resolution of fpVCT resulted in reduced partial volume and metal beam-hardening artefacts. This facilitated assessment of vascular lumen in the presence of calcified plaque and evaluation of fractures, especially in the presence of fixation hardware. Evaluation of arteriovenous malformation using dynamic fpVCT angiography was of limited utility. Dynamic CTA using fpVCT can visualize time-varying phenomena in neuro and lower limb vascular applications and has suffcient diagnostic imaging quality to evaluate a number of pathologies affecting these regions. • CTA using fpVCT has sufficient spatial and temporal resolution to study phasic blood flow. • CTA using fpVCT reveals recurrence of aneurysms even after clipping/coiling. • fpVCT has reduced partial volume and metal beam-hardening artefacts. • fpVCT can show vessel lumen in the presence of calcified plaque. • CTA using fpVCT can demonstrate vascular supply to transplanted grafts.

A theoretical framework for quantifying blood volume flow rate from dynamic angiographic data and application to vessel-encoded arterial spin labeling MRI

Angiographic methods can provide valuable information on vessel morphology and hemodynamics, but are often qualitative in nature, somewhat limiting their ability for comparison across arteries and subjects. In this work we present a method for quantifying absolute blood volume flow rates within large vessels using dynamic angiographic data. First, a kinetic model incorporating relative blood volume, bolus dispersion and signal attenuation is fitted to the data. A self-calibration method is also described for both 2D and 3D data sets to convert the relative blood volume parameter into absolute units. The parameter values are then used to simulate the signal arising from a very short bolus, in the absence of signal attenuation, which can be readily encompassed within a vessel mask of interest. The volume flow rate can then be determined by calculating the resultant blood volume within the vessel mask divided by the simulated bolus duration. This method is applied to non-contrast magnetic resonance imaging data from a flow phantom and also to the cerebral arteries of healthy volunteers acquired using a 2D vessel-encoded pseudocontinuous arterial spin labeling pulse sequence. This allows the quantitative flow contribution in downstream vessels to be determined from each major brain-feeding artery. Excellent agreement was found between the actual and estimated flow rates in the phantom, particularly below 4.5 ml/s, typical of the cerebral vasculature. Flow rates measured in healthy volunteers were generally consistent with values found in the literature. This method is likely to be of use in patients with a variety of cerebrovascular diseases, such as the assessment of collateral flow in patients with steno-occlusive disease or the evaluation of arteriovenous malformations.

Susceptibility-weighted imaging in the evaluation of brain arteriovenous malformations

Digital subtraction angiography (DSA) remains the gold standard in the evaluation of arteriovenous malformations (AVMs). Susceptibility-weighted imaging (SWI), a relatively new magnetic resonance imaging (MRI) technique, exploits the magnetic susceptibility differences of various tissues, such as blood, iron and calcification. Earlier studies have shown that the magnitude and phase information of SWI offers improved sensitivity, revealing low-flow vascular malformations that are invisible on conventional gradient-echo (GRE) sequences. To evaluate the imaging appearance of AVMs on SWI. In this retrospective study, the appearance of the various components (feeding artery, nidus, and draining veins) of AVMs on the phase, magnitude, and minimal intensity projection (minIP) images of SWI were analyzed in 14 patients with AVM and compared with conventional sequences. Detection and delineation of various components of AVMs was best achieved in the magnitude images. Although minIP was most effective in detecting hemorrhage and calcification, it was the magnitude image that could separate the hemorrhagic and calcified component in the nidus from the remaining nidus. The minIP was less effective in detecting the AVM components, especially nidus and draining vein, whereas conspicuity was poor with the phase images. The magnitude images of the SWI help in differentiating the different components of AVM and also helps in differentiating nidus from hemorrhage and calcification.

Assessment of arteriovenous malformations with 3-Tesla time-resolved, contrast-enhanced, three-dimensional magnetic resonance angiography

Although conventional catheter angiography is commonly used in the evaluation of intracranial arteriovenous malformations (AVMs), less invasive tools are more suitable for screening or follow-up. Older MR angiography techniques cannot provide high enough temporal and spatial resolution for assessing AVMs. Threetesla time-resolved imaging of contrast kinetics (TRICKS)-a time-resolved, contrast-enhanced 3D MR angiography technique-achieves subsecond time resolution without sacrificing spatial resolution. The purpose of this study was to assess the accuracy of TRICKS at 3 T in the evaluation of AVMs. Between November 2006 and November 2007, 31 patients who were known to have AVMs underwent evaluation in a 3-T unit with the TRICKS technique. The TRICKS images were then evaluated independently by 2 radiologists for nidus detection, early venous filling detection, and Spetzler-Martin classification, and these results were compared with the results of catheter angiography. Time-resolved imaging of contrast kinetics achieved 96% sensitivity and 100% specificity both in nidus detection and early venous filling detection. The Spetzler-Martin grades also showed excellent correlation with catheter angiography findings (kappa= 0.89). Although this is a preliminary study, the authors' results indicate that time-resolved contrast-enhanced 3D MR angiography at 3 T is a good tool to assess AVMs, and has the potential to replace catheter angiography in screening or follow-up examinations of patients with AVMs.

Recurrent Caudate Hemorrhage Caused by an Occult Arteriovenous Malformation Evaluation of Patients With Recurrent Hemorrhage

Recurrent Caudate Hemorrhage Caused by an Occult Arteriovenous Malformation Evaluation of Patients With Recurrent Hemorrhage

Evaluation of Arteriovenous Malformations (AVMs) With Transcranial Color-Coded Duplex Sonography

The clinical value of transcranial color-coded duplex sonography (TCCS) in the evaluation of arteriovenous malformations (AVMs) has not yet been fully investigated. In this study, 54 intracranial AVMs confirmed by angiography were prospectively examined over 6 years. The purpose of the study was to describe their typical sonographic features and to define sensitivity for diagnosis with regard to the location of an AVM. Transcranial color-coded duplex sonographic findings for 54 patients with intracranial AVMs are presented. The vessels of the circle of Willis were identified by location, course, and direction of flow on color flow images. In accordance with digital subtraction angiography, the intracranial AVMs could be visualized in 42 cases (sensitivity, 77.8%). The pathologic vessels were coded in different shades of blue and red, corresponding to varying blood flow directions in the AVM. The major feeding vessels could be easily identified. Hemodynamic parameters showing increased systolic and diastolic flow velocities and a decreased pulsatility index were better attainable with TCCS than with conventional transcranial Doppler sonography. Arteriovenus malformations located near the cortex, that is, in the parietal, frontal, occipital, and cerebellar regions of the brain, could not be visualized. In contrast, AVMs located in the basal regions were very easy to image (sensitivity, 88.9%). Additionally, TCCS proved useful for follow-up examinations postoperatively or after embolization. Transcranial color-coded duplex sonography is a valuable noninvasive method for the diagnosis and long-term follow-up of intracranial AVMs. Arteriovenous malformations located in the axial imaging plane can be more easily detected. Nevertheless, TCCS should not be used as a screening method.

Applications de l’arm dynamique dans la pathologie vasculaire du système nerveux central

Conventional catheter angiography (CCA) remains the gold standard for the evaluation of most intracranial vascular malformations. MRA techniques such as Time of Flight, Phase Contrast or 3D contrast-enhanced MRA, provide anatomic evaluation but without hemodynamic information. Recently developed, dynamic MRA is based on dynamic acquisition of images and image subtraction; these two principal characteristics produce images comparable to those obtained by CCA. The purpose of this review is to explain the principles, advantages and drawbacks of this technique in the evaluation of arteriovenous malformations, arteriovenous fistulas, aneurysms and venous thrombosis.

P012: Prenatal 3D color-Doppler angiography is superior to MRI in the evaluation of arteriovenous malformation of vein of Galen

P012: Prenatal 3D color-Doppler angiography is superior to MRI in the evaluation of arteriovenous malformation of vein of Galen

MAGNETIC RESONANCE ANGIOGRAPHY OF VASCULAR MALFORMATIONS

The rapid advancement of MR angiography techniques over the past few years has brought this imaging modality to the forefront in the diagnosis and management of vascular diseases of the central nervous system. The ability to acquire a three-dimensional dataset in a single acquisition and display these data using a number of different postprocessing techniques has made MR angiography especially useful in the evaluation of arteriovenous malformations (AVMs) before radiosurgery. In many instances, MR angiography has replaced conventional angiography for the purpose of radiosurgery treatment planning and follow-up. As this technology continues to advance, it will undoubtedly play an even more important role in the management of vascular malformations in the future.