Secondary Logo

Journal Logo

Scientific Research (Molecular, Genetic, Histologic)

Precontrast Magnetic Resonance Imaging Findings and Assessment of Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Low- and High-Flow Vascular Malformations

Berger, Sigurda,b; Andersen, Runea; Jakobsen, Jarl Åsbjørna,b; Geier, Oliver Marcela; Abildgaard, Andreasa; Dorenberg, Erica,b

Author Information
Journal of Vascular Anomalies: September 2021 - Volume 2 - Issue 3 - p e019
doi: 10.1097/JOVA.0000000000000019
  • Open

Abstract

Introduction

Vascular malformations are heterogeneous, benign lesions that may cause severe morbidity. Based on angioarchitecture and flow dynamics, vascular malformations are classified into 2 main categories: high-flow lesions like arteriovenous malformations (AVM) and arteriovenous fistula (AVF), and low-flow lesions like venous malformations (VM) and lymphatic malformations. Patients may also present with combined vascular malformations like lymphatic-venous malformations (LVM), as well as other combinations.1 To achieve a good treatment outcome, it is essential to classify and diagnose vascular malformations correctly, and a thorough diagnostic workup is mandatory before initiation of treatment. This includes patient history, clinical evaluation, radiological imaging, as well as genetic testing in certain cases.2,3

Magnetic resonance imaging (MRI) is valuable for evaluation of vascular malformation because of its excellent soft tissue contrast that provides detailed information about tissue layer involvement and distribution.4 The presence of phleboliths, as a result of thrombus formation due to stagnant blood flow, is reported as being pathognomonic of VM, whereas depiction of tortuous vessels with flow voids may predict high-flow malformations like AVM.5–7 To assess flow dynamics, time resolved MRI angiography and delayed contrast-enhanced imaging may be useful. To differentiate high-flow from low-flow malformations, flow parameters like “artery-lesion enhancement time” (ALET) and “contrast rise time/enhancement time” have been introduced.8–10 However, in all studies, a considerable overlap between high-flow and low-flow malformations was found regarding ALET, suggesting the existence of a group of “early-enhancing” VM. The use of delayed contrast-enhanced imaging with breath-hold technique up to 10 minutes after contrast administration has been reported,4,11,12 but to our knowledge, no systematic evaluation of both high- and low-flow lesions with this approach has yet been performed.

In this study, we aimed to evaluate MRI findings in vascular malformations in a cohort of patients referred to a national treatment center by assessing (1) the prevalence of phleboliths and flow voids and (2) dynamic contrast enhancement characteristics of vascular malformations in early and delayed contrast phases.

Patients and methods

The study was conducted at our national treatment center for vascular anomalies. Between September 2011 and July 2014, patients at the age of 12 years and above that were consecutively referred to our center with a suspected diagnosis of AVM, AVF, VM, or LVM were invited to participate. Exclusion criteria were (1) renal failure (females with serum creatinine >110 μmol/L, males with serum creatinine >120 μmol/L), (2) claustrophobia, (3) hypersensitivity to contrast media, (4) pregnancy, and (5) no evidence of AVM, AVF, VM, or LVM after diagnostic workup.

One hundred and two patients were recruited. Before study analyses, all patients were routinely evaluated by clinical examination, ultrasound, and MRI. The malformations were classified according to the International Society for the Study of Vascular Anomalies classification,1 based on certain clinical and imaging findings (Table 1). Two patients with cystic lesions, 1 patient with tumor and 1 patient with a purely lymphatic malformations were excluded after diagnostic workup; hence 98 patients were available for study analyses.

Table 1. - Clinical and Imaging Characteristics of Vascular Malformations, According to Routine Clinical Practice in Our Institution
Low-flow malformations
 Venous malformation Clinical: soft, compressible mass with blue discoloration in superficial lesions.
Ultrasound: mass with compressible vascular spaces. Slow flow pattern with Doppler ultrasound.
MRI: lesions with high STIR signal and low T1 signal. Presence of phleboliths. Slow contrast enhancement with dynamic angiography.
 Lymphatic-venous malformation As venous malformation, but to varying degree presence of vascular spaces with absent Doppler signals with ultrasound and absent contrast enhancement with MRI.
High-flow malformations
 Arteriovenous malformation Clinical: warm compressible mass with palpable thrill or pulse.
Ultrasound: vessels with low-resistance pulsatile flow with Doppler ultrasound.
MRI: diffuse lesions, frequently with flow voids on SE sequences. Rapid contrast enhancement of dilated feeders and early venous return seen with dynamic angiography.
Angiography: rapid enhancement and the presence of arteriovenous shunting.
 Arteriovenous fistula Clinical: variable clinical presentation. Palpable thrill or pulse may be present.
Ultrasound: direct communication between artery and vein. Pulsatile, low-resistance venous flow seen with Doppler ultrasound.
MRI: direct arteriovenous connection and early venous return seen with dynamic MRI angiography.
Abbreviations: MRI, magnetic resonance imaging; SE, spin echo; STIR, short tau inversion recovery.

The MRI images obtained during diagnostic workup were the basis of the analyses in this study. The images were reviewed independently by 2 radiologists in the multidisciplinary team for vascular anomalies in our institution. They were blinded to the clinical information and diagnosis. In cases of disagreement, consensus reading with a senior radiologist specialized in MRI was performed.

Written informed consent was obtained from all patients and the study was approved by the regional ethics committee.

MRI protocol

MRI was performed on a 1.5 T scanner (Magnetom Avanto, Siemens, Erlangen, Germany). Patient positioning and coil selection was adapted to lesion localization. The protocol included the following sequences (see Table 2 for basic MR sequence parameters):

Table 2. - MRI Sequences
STIR T1 TR-MRA (“TWIST”) T1 FS (“VIBE”)
Sequence type IR/SE SE GR GR
Acquisition type 2D 2D 3D 3D
Slice thickness (mm) 4–5 4–5 2–3 1.3–1.8
Slice center spacing (mm) 4.4–7 4.4–7 2–3 1.3–1.8
Repetition time (ms) 6000 600 5.4 2.5
Echo time (ms) 81 9 1.6–1.8 0.9–1.0
Echo train length 11 3 1 1
Number of averages 1 1–3 1 1
Pixel bandwidth (Hz) 130 171 302 651
Flip angle 150 130–150 25 25
Pixel spacing (row and column, mm) 0.5–1.2 0.6–1.3 0.9–1.8 1.3–1.7
Abbreviations: FS, fat-sat; GR, gradient echo; IR, inversion recovery; MRI, magnetic resonance imaging; SE, spin echo; STIR, short tau inversion recovery; TR-MRA, time-resolved MRI angiography; TWIST, Time Resolved Angiography With Interleaved Stochastic Trajectory; VIBE, volumetric interpolated breath-hold examination.

  1. Short tau inversion recovery (STIR) and T1-weighted sequence in 2 orthogonal planes, for depiction of anatomical distribution.
  2. Time-resolved 3-dimensional (3D) MR angiography (TR-MRA) for depiction of rapid flow dynamics, using the “TWIST” sequence (Time resolved angiography With Interleaved Stochastic Trajectory).13 This sequence is based on partial k-space filling, combining successive partial k-space data with an initial, complete k-space acquisition. For this study, the initial, full k-space filling was acquired in approximately 12 seconds, followed by new partial k-space acquisitions every 3 seconds; in some cases, this was increased up to 3.3 seconds to acquire sufficient slices for anatomical coverage. The central sampling fraction of k-space data was 15%. Total acquisition time for TR-MRA was approximately 110 seconds. Additional, interleaved image series were reconstructed from the k-space data, resulting in an effective temporal resolution of 1.5–1.65 seconds, and a total of approximately 60 image series.
  3. Fat-suppressed T1 3D GRE sequence for depiction of successive lesion enhancement and washout, using the “VIBE” sequence (volumetric interpolated breath-hold examination).

The STIR and T1 sequences were acquired before injection of intravenous contrast medium, as was a baseline VIBE acquisition for image subtraction, and a test run of the TR-MRA. Injection of contrast medium was initiated directly after the first complete k-space filling of the TR-MRA. The contrast medium was gadoterate meglumine 0.5 mmol/mL (Dotarem, Guerbet, France or Clariscan, GE Healthcare, Oslo, Norway). A dose of 0.2 mL/kg body weight was administered, with flow rate adjusted to provide a total injection time between 8 and 11 seconds, followed by a 25 mL saline chaser. After completion of the TR-MRA, the VIBE sequence was run every minute from 2 to 15 minutes after contrast medium injection (Figure 1).

Figure 1.
Figure 1.:
Precontrast and contrast-enhanced imaging of venous malformation in the lower extremity. Arrows showing areas of contrast accumulation. A, Axial STIR image showing the extent of the malformation, (B) VIBE image precontrast, (C) contrast-enhanced VIBE image 2 min postinjection, and (D) 15 min postinjection. STIR indicates short tau inversion recovery; VIBE, volumetric interpolated breath-hold examination.

Maximum intensity projections (MIPs) of the TR-MRA series were obtained in 3 orthogonal planes, after subtraction with baseline series. The MIPs were used for assessment of contrast enhancement dynamics such as ALET. When improved depiction of vascular anatomy was needed, 3D models (MIP and volume rendering) were made from individual TR-MRA image series.

The baseline precontrast VIBE series was subtracted from the 2- and 15-minute series to depict occurrence of contrast accumulation at these time points. In addition, mutual subtractions of the 2- and 15-minute series (2–15 and 15–2) were performed to delineate contrast medium disappearance and appearance between 2 and 15 minutes after injection (Figure 2).

Figure 2.
Figure 2.:
VIBE subtraction images of venous malformation (same as in Figure 1). A, 2 min postinjection minus precontrast showing contrast accumulation in small foci at 2 min (arrows), (B) 15 min postinjection minus precontrast showing larger areas in the malformation accumulating contrast at 15 min (arrow), (C) 15 min minus 2 min showing contrast accumulation between 2 and 15 min postinjection (arrow), and (D) 2 min minus 15 min showing only discrete washout of contrast between 2 and 15 min postinjection (arrow). VIBE indicates volumetric interpolated breath-hold examination.

The circulation time from start of injection until arrival in the lesion region varied substantially between patients, reflecting the variation in lesion location and patient hemodynamics. Therefore, the acquisition duration after arrival of contrast medium (hereafter termed observation time) varied considerably among patients.

MRI evaluation

  1. Location of the lesion was classified as one or more of the following: upper extremity, lower extremity, trunk, and head and neck region.
  2. Tissue involvement was classified as one or more of the following: subcutaneous tissue, muscle, bone, intrathoracic, and intra-abdominal.
  3. Phleboliths were defined as a rounded, sharply demarcated signal voids within the lesion on STIR and T1 (Figure 3A). Due to disagreement between primary readers, presence or absence of phleboliths was evaluated by consensus reading in 16 of 98 (16.3%) cases.
  4. Flow voids were defined as a tubular signal voids centrically along vascular structures within the lesion on noncontrast enhanced sequences (Figure 4). Consensus reading regarding flow void was performed in 28 of 98 (28.6%) cases.
  5. ALET was defined as the time interval (seconds) between observable contrast enhancement in a named, normal artery at the level of the malformation, and observable lesion enhancement, assessed on TR-MRA.
  6. Contrast accumulation was defined as observable signal increase in one or more regions within the lesion. This was evaluated semiquantitatively on VIBE images, using subtraction techniques described earlier. We analyzed accumulation in predefined time-intervals: (1) between preinjection and 2 minutes postinjection, (2) between preinjection and 15 minutes postinjection, and (3) between 2 minutes postinjection and 15 minutes postinjection. The readers answered “yes” or “no,” depending on whether contrast accumulation was observed or not. Consensus reading regarding contrast accumulation was performed in 8 of 89 (9.0%) available cases.
  7. Contrast washout was defined as observable signal decrease in one or more regions between 2 minutes postinjection and 15 minutes postinjection, evaluated semiquantitatiively on VIBE images. The readers answered “yes” or “no,” depending on whether contrast wash-out was observed or not. Consensus reading regarding washout was performed in 12 of 89 available (13.5%) cases.
Figure 3.
Figure 3.:
Phleboliths. A, Venous malformation of the face. Phlebolith with rounded signal void on STIR and T1 (arrow). B, Venous malformation of the forearm. Phlebolith with rounded signal void on STIR and “eggshell” appearance on T1 (arrow). STIR indicates short tau inversion recovery.
Figure 4.
Figure 4.:
AVM of the hand. A, Time-resolved MR angiography showing a dilated feeder from the ulnar artery (arrow), (B) corresponding flow void (arrow) on T1. AVM indicates arteriovenous malformations; MR, magnetic resonance.

Statistical methods

Categorical variables are presented as counts and percentages, continuous variables as median values and ranges. To compare categorical variables, Fisher exact test was used. For continuous variables, we used Mann-Whitney U test as the data, according to the Shapiro Wilk test of normality, were not normally distributed. Kappa statistics was performed to determine interobserver agreement for the imaging biomarkers phleboliths and flow voids. P values <.05 were considered statistically significant. All tests were 2 sided. All analyses were conducted using IBM SPSS statistics, version 25.

Results

The demographic data, diagnoses, and anatomical distribution are summarized in Table 3. The MRI evaluation of low- and high-flow malformations are summarized in Table 4.

Table 3. - Demographic Data, Diagnosis, and Anatomical Distribution
Age (Median, Range) 27 y (12–64)
Categories n (%)
Sex Male 38 (38.8)
Female 60 (61.2)
Diagnosis* Venous malformation 86 (87.8)
AV malformation 8 (8.2)
Arteriovenous fistula 1 (1.0)
Lymphatic-venous malformation 3 (3.1)
Anatomical location Head and neck region 19 (19.4)
Upper extremity 20 (20.4)
Trunk 9 (9.2)
Lower extremity 50 (51.0)
Tissue Subcutis 28 (28.6)
Muscle 27 (27.6)
Subcutis and muscle 32 (32.7)
Subcutis, muscle, and bone 6 (6.1)
Muscle and bone 3 (3.1)
Bone 1 (1.0)
Subcutis, muscle, and intra-abdominal 1 (1.0)
Categorical data described as counts and percentages.
Abbreviation: AV, arteriovenous.
*Based on diagnostic workup before study analyses, see Table 1.

Table 4. - MRI Evaluation of High- and Low-Flow Malformations*
High-Flow Low-Flow P
Phleboliths 0/9 (0%) 12/89 (13.5%) .60
Flow voids 5/9 (55.6%) 15/89 (16.9%) <.05
Median ALET (range) 0.8 s (0–6.3) 9.2 s (0–35.1)† <.05
Contrast accumulation 2 min 8/8 (100%) 79/81 (97.5%) 1.0
Contrast accumulation 15 min 8/8 (100%) 80/81 (98.8) 1.0
Contrast accumulation between 2 and 15 min 5/8 (62.5%) 75/81 (92.6%) <.05
Washout between 2 and 15 min 4/8 (50%) 15/81 (18.1%) .06
Combination of accumulation and  washout 2–15 min 2/8 (25.0%) 14/81 (17.3%) 1.0
Abbreviations: ALET, artery-lesion enhancement time; MRI, magnetic resonance imaging.
*Evaluation of predefined criteria described under Methods.
†25 “non-enhancing” low-flow malformations excluded from analysis.

Ninety-eight cases were available for precontrast analyses (low-flow n = 89, high-flow n = 9). In 8 of the cases (8.2%), we were unable to obtain sufficient TWIST or VIBE images, due to technical issues and/or lack of patient compliance (VM n = 6, AVM n = 1, LVM n = 1). Further, 1 case was excluded due to susceptibility artifacts (VM), leaving 89 cases available for contrast analyses (low-flow n = 81, high-flow n = 8). In 25 of these 89 (28.1%) malformations, no lesion enhancement was observed on TR-MRA. The observation time in these cases ranged from 36.0 to 85.2 seconds. Of the remaining 64 of 89 (71.9%) malformations, the median ALET was 7.8 seconds (range 0–35.1).

Precontrast MRI evaluation of low- and high-flow malformations (n = 98)

Phleboliths were present in 12 of 89 (13.5%) low-flow malformations, and 0 of 9 (0%) high-flow malformations (P = .60). Flow voids were detected in 15 of 89 (16.9%) low-flow malformations and 5 of 9 (55.6%) high-flow malformations (P < .05). There were no significant differences regarding sex, age, and anatomical distribution between the malformation types. A subanalysis of low-flow malformations showed that phleboliths were present in 11 of 65 (16.9%) malformations involving musculature and in 1 of 24 (4.2%) malformations without muscle involvement (P = .17).

The interobserver agreement was kappa 0.42 for phleboliths and 0.16 for flow voids.

Dynamic contrast-enhanced MRI characteristics of low- and high-flow malformations (n = 89)

Of the 64 malformations with observable lesion enhancement on TR-MRA, the median ALET of low flow malformations (n = 56) was 9.2 seconds (range 0–35.1) and of high-flow malformations (n = 8) was 0.8 seconds (range 0–6.30) (P < .05). In 21 of 81 (25.9%) low-flow malformations, we observed an ALET that overlapped with ALET of high-flow malformations (≤6.3 seconds). The 25 nonenhancing lesions were all low-flow malformations.

Contrast accumulation between preinjection and 2 minutes postinjection was observed in 79 of 81 (97.5%) low-flow malformations and 8 of 8 (100%) high-flow malformations, whereas contrast accumulation between preinjection and 15 minutes postinjection was observed in 80 of 81 (98.8%) low-flow malformations and 8 of 8 (100%) high-flow malformations. Contrast accumulation between 2 and 15 minutes postinjection was observed in 75 of 81 (92.6%) low-flow malformations and in 5 of 8 (62.5%) high-flow malformations (P < .05). Wash-out between 2 and 15 minutes postinjection was observed in 15 of 81 (18.5%) low-flow malformations and 4 of 8 (50%) high-flow malformations (P = .06). A combination of contrast accumulation and wash-out between 2 and 15 was observed in 14 of 81 (17.3%) low-flow malformations and 2 of 8 (25%) high-flow malformations (P = 1).

Discussion

In the present study, we assessed certain MRI characteristics of vascular malformations in a large patient cohort, focusing on phleboliths, flow voids, and dynamic contrast-enhanced imaging. We performed a systematic evaluation of contrast accumulation characteristics up to 15 minutes after contrast administration.

In our material, phleboliths were observed infrequently with a prevalence of 13.5% in low-flow malformations and 0% in high-flow malformations. This indicates specificity of phleboliths as a diagnostic marker for low-flow malformations. However, due to the low number of high-flow lesions and lack of statistical power, this finding cannot be attributed significance. Interestingly, 92% of low-flow malformations with phleboliths involved muscular tissue. Dompmartin et al14 reported that VM with muscular involvement are associated with localized intravascular coagulopathy, which may lead to increased clotting and thrombus formation. This observation was supported by Vogel et al15 who found a significantly higher prevalence of phleboliths in intramuscular VM than in extramuscular malformations and hypothesized that minor trauma and repeated muscular contraction may facilitate higher levels of oxidative waste products and increased prothrombotic clotting factors.

According to previous reports,6,16 phleboliths appear dark on all sequences, whereas thrombi may present with high signal on T1-weighted images. In some cases, we observed an “eggshell” appearance with rounded signal void on STIR and corresponding ring-shaped signal void with bright central signal on T1 (Figure 3B), possibly due to partial thrombus calcification. This led to disagreement between the primary readers, which may explain the moderate interobserver agreement (kappa 0.42). After consensus reading, such signal changes were classified as phleboliths.

The presence of flow voids in high-flow malformations was low (55.6%), although significantly more frequent than in low-flow malformations (16.9%). Flow voids have traditionally been considered a reliable sign of high-flow malformations. However, the low sensitivity and non-specificity of flow voids in diagnosing high-flow malformations in our material is in accordance with previous reports.8–10 This may reflect the vascular heterogeneity of vascular malformations; flow velocity within both high- and low-flow lesions may be highly variable. Furthermore, the ability of MRI to display flow voids may depend on malformation size and vessel diameter, as well as the sequence type and sequence parameters used in the protocol. In our experience, flow voids in large vessels are rarely misinterpreted, whereas flow voids in small vessels are more challenging and may be difficult to separate from fibrous striations, thrombosed vessels, and sometimes chemical shift artifacts. This may have caused the poor interobserver agreement (kappa 0.16) in our material. We believe that the use of flow voids as imaging biomarkers may be helpful, but should be done with caution due to possible pitfalls, particularly in vessels with small diameters.

We revealed considerable variations in contrast enhancement characteristics with TR-MRA. In 25 of the 81 low-flow malformations, no lesion enhancement was observed, suggestive of a subgroup of malformations with slow venous inflow, not detectable on TR-MRA. However, in nearly all lesions (92%), we observed contrast accumulation at the 2 minutes postcontrast VIBE images. In such cases, we should be aware of the observation time, which ranged from 36 to 82.2 seconds. In lesions with short observation time, contrast enhancement may have been missed on TR-MRA.

The range of ALET in the contrast-enhancing malformations was 0–35.1 seconds, and as expected, median ALET was significantly higher in low-flow malformation than in high-flow malformations. In 25.9% of low-flow malformations, we observed an ALET that overlapped with ALET of high-flow malformations (≤6.3 seconds). Based on these observations, we identified 3 distinct subtypes of low-flow malformations, reflecting differences in enhancement characteristics with TR-MRA: (1) arterial inflow, defined as malformations with ALET ≤6.3 (n = 21), (2) no arterial inflow, defined as malformations with ALET >6.3 seconds (n = 35), and (3) nonenhancing with no lesion enhancement on TWIST (n = 25). No significant differences regarding flow voids and phleboliths were found between the subtypes. Contrast accumulation between 2 and 15 minutes was less frequent in nonenhancing lesions than in enhancing lesions. The characteristics of low-flow malformation subtypes are summarized in Table 5.

Table 5. - MRI Evaluation of Low-Flow Malformations Subtypes*
Arterial Inflow No Arterial Inflow Nonenhancing P
Phleboliths 6/21 (28.6%) 3/35 (8.6%) 3/25 (12%) .14
Flow voids 4/21 (19%) 7/35 (20%) 2/25 (8%) .44
Median ALET (range) 4.9 s (0–6.3) 11.1 s (7.5–35.1) - <.05
Contrast accumulation 2 min 21/21 (100%) 35/35 (100%) 23/25 (92.0%) .16
Contrast accumulation 15 min 21/21 (100%) 35/35 (100%) 24/25 (96%) .57
Contrast accumulation between 2 and 15 min 21/21 (100%) 34/35 (97.1%) 20/25 (80.0%) <.05
Washout between 2 and15 min 6/21 (28.6%) 6/35 (17.1%) 3/25 (12%) .36
Abbreviations: ALET, artery-lesion enhancement time; MRI, magnetic resonance imaging.
*Evaluation of predefined criteria described under Methods.

The observation of early enhancing low-flow malformations is in accordance with previous reports; early opacification of low-flow malformations was described already in 1983 by Burrows et al.17 Based on a theory that some VM filled via dilated capillaries, they classified such lesions as capillary VM. However, this term may be misleading as a capillary VM is a combination of a VM and cutaneous capillary malformations, according to the updated International Society for the Study of Vascular Anomalies classification.1 Hammer et al18,19 recently described hemodynamic characteristics of 83 vascular malformations at 3T MRI and identified a subgroup of VM with early lesion enhancement on time-resolved MRI angiographic images. They classified this subgroup as VM with “AV-microshunts” and found correlation between “AV microshunts” and the number of phleboliths. They suggested that this phenomenon may be the result of a natural healing process after thrombosis. In our material, phleboliths were more frequent in the group of low-flow malformations with “arterial inflow,” but no significant difference could be confirmed.

The size of arterial feeders in vascular malformations may vary considerably. In AVMs, the feeders have traditionally been described as large, torturous vessels,11 whereas feeders in early enhancing low-flow malformations, in our experience, may be small or not visible at all. To our knowledge, no systematic evaluation of arterial feeder size in high- and low-flow malformations has been reported, and such analyses would be of interest. In our material, however, the combination of often very small arterial feeders and image noise in subtracted contrast-enhanced images provided unreliable diameter measures. With improved imaging protocols which may facilitate better image quality and more precise size estimates of small vessels, assessment of arterial feeder size should be included in future studies.

Despite the information provided from TR-MRA in the early contrast phases, delayed contrast-enhanced imaging seems to be of value to confirm vascularity in low-flow malformations with limited or absent contrast enhancement on TR-MRA. In our material, nearly all low-flow malformations accumulated contrast between preinjection and 2 minutes postinjection and between preinjection and 15 minutes postinjection. In a minority of the low-flow malformations (17.3%), we observed flow heterogeneity with a combination of contrast accumulation and washout between 2 and 15 minutes postinjection. The findings confirm that low-flow malformations consist of slow-flowing vascular components that accumulate blood over a long period of time. This was also shown in a study by Caty et al12; they analyzed perfusion of VM using VIBE imaging at the time points 0, 1, 5, and 10 minutes. Enhancement was assessed both manually and with semiautomated software analyzing pixel enhancement, after segmentation of the malformation. They found increasing contrast enhancement in VM between the time points 0 and 10 minutes, at pretreatment imaging. Malformations that clinically responded to treatment seemed to have higher perfusion percentage at 10 minutes postinjection. Regarding high-flow malformations, contrast accumulation was observed in all 8 lesions between preinjection and 2 minutes postinjection, and between preinjection and 15 minutes postinjection. Unexpectedly, contrast accumulation was observed in 5 lesions between 2 and 15 minutes postinjection. Washout was only observed in 4 of the 8 high-flow malformations between 2 and 15 minutes postinjection. Regarding the hemodynamic nature of high-flow malformations with rapid flow and AV-shunting, we expected to see a clear pattern of contrast washout after 2 minutes, and not contrast accumulation as observed in our material. According to previous publications,20,21 some high-flow malformation may exhibit features of a vascular tumor with perilesional T2 hyperintensity, mass effect, and contrast enhancement in the surrounding stroma, which may be related to edema and fibrofatty changes. This should be taken into account in MRI evaluation of high-flow malformations, especially in small AVMs where dysplastic vessels and surrounding tissue may be difficult to separate, and may explain the high prevalence of contrast accumulating AVMs in the present study. Our findings imply a considerable heterogeneity of flow dynamics in high-flow malformations, and indicate that slow flowing vascular components in such lesions may exist. Importantly, delayed postcontrast imaging with evaluation methods described in the present study seems unable to discriminate low- and high-flow malformations.

Our method utilizing contrast-enhanced VIBE imaging with subtraction techniques may have introduced certain technical biases. The calculation of MRI image pixel grayscale values is based on the distribution of signal values in the whole slice. Theoretically, this may influence the displayed signal of a malformation, which depends both on signal effects in the surrounding tissue, as well as intrinsic signal effects. For malformations in proximity of intensely enhancing structures, the displayed signal may have been affected by scanner adjustments, which may have led to underestimation of contrast accumulation. Such effects may also apply in malformations consisting partially of intensely enhancing vessels, typically observed at 2 minutes postinjection, in which the signal of surrounding, less enhancing malformation tissue may be “falsely” low. It is though unlikely that our results were severely affected, because the vast majority of the malformations were surrounded by nonenhancing tissue like musculature and fat. Further, the combination of visually clear contrast effects and a very simple classification grouping the malformations into only 2 categories provided a qualitative method which, in our opinion is valid for the purpose of this study. However, to minimize the effects of such potential biases, the use of automated software as described by Caty et al,12 as well as measurements of contrast to noise ratio and signal to noise ratio, may be beneficial.

The major limitation of this study is the low number of patients with high-flow malformations in our material. A higher number of high-flow malformations would have provided more statistical power and better precision in our analyses. However, the number of included patients with AVM in this consecutive designed study reflects the expected low prevalence of this condition. Also, evaluation of contrast enhancement characteristics was performed by 2 radiologists, using predefined parameters. Computer-aided, quantitative methods have been introduced in several publications and may provide more reliable analyses. Using such computer applications can though be time-consuming and may not yet be applicable in clinical work.

In conclusion, phleboliths and flow voids seem to be infrequent MRI findings in vascular malformations. Importantly, flow voids were detected both in high- and low-flow malformations and may have poor diagnostic value. Regarding contrast enhancement patterns, we found a considerable overlap between low- and high-flow malformations, and surprisingly, in a majority of high-flow malformations, we observed successive contrast accumulation up to 15 minutes after contrast administration. Our findings indicate that vascular heterogeneity exists within both types of malformations, which should be taken into account in MRI evaluation of this patient group.

References

1. Dasgupta R, Fishman SJ. ISSVA classification. Semin Pediatr Surg. 2014;23:158–161.
2. Alomari A, Dubois J. Interventional management of vascular malformations. Tech Vasc Interv Radiol. 2011;14:22–31.
3. Nguyen HL, Boon LM, Vikkula M. Vascular anomalies caused by abnormal signaling within endothelial cells: targets for novel therapies. Semin Intervent Radiol. 2017;34:233–238.
4. Dubois J, Alison M. Vascular anomalies: what a radiologist needs to know. Pediatr Radiol. 2010;40:895–905.
5. Ernemann U, Kramer U, Miller S, et al. Current concepts in the classification, diagnosis and treatment of vascular anomalies. Eur J Radiol. 2010;75:2–11.
6. Merrow AC, Gupta A, Patel MN, Adams DM. 2014 revised classification of vascular lesions from the international society for the study of vascular anomalies: radiologic-pathologic update. Radiographics. 2016;36:1494–1516.
7. Bashir U, Shah S, Jeph S, O’Keeffe M, Khosa F. Magnetic resonance (MR) imaging of vascular malformations. Pol J Radiol. 2017;82:731–741.
8. Ohgiya Y, Hashimoto T, Gokan T, et al. Dynamic MRI for distinguishing high-flow from low-flow peripheral vascular malformations. AJR Am J Roentgenol. 2005;185:1131–1137.
9. Kociemba A, Karmelita-Katulska K, Stajgis M, Oszkinis G, Pyda M. Distinguishing high-flow from low-flow vascular malformations using maximum intensity projection images in dynamic magnetic resonance angiography - comparison to other MR-based techniques. Acta Radiol. 2016;57:565–571.
10. van Rijswijk CS, van der Linden E, van der Woude HJ, van Baalen JM, Bloem JL. Value of dynamic contrast-enhanced MR imaging in diagnosing and classifying peripheral vascular malformations. AJR Am J Roentgenol. 2002;178:1181–1187.
11. Flors L, Leiva-Salinas C, Maged IM, et al. MR imaging of soft-tissue vascular malformations: diagnosis, classification, and therapy follow-up. Radiographics. 2011;31:1321–1340.
12. Caty V, Kauffmann C, Dubois J, et al. Clinical validation of semi-automated software for volumetric and dynamic contrast enhancement analysis of soft tissue venous malformations on magnetic resonance imaging examination. Eur Radiol. 2014;24:542–551.
13. Lim R, Shapiro M, Wang E, et al. 3D time-resolved MR angiography (MRA) of the carotid arteries with time-resolved imaging with stochastic trajectories: comparison with 3D contrast-enhanced bolus-chase MRA and 3D time-of-flight MRA. Am J Neuroradiol. 2008;29:1847–1854.
14. Dompmartin A, Acher A, Thibon P, et al. Association of localized intravascular coagulopathy with venous malformations. Arch Dermatol. 2008;144:873–877.
15. Vogel SA, Hess CP, Dowd CF, et al. Early versus later presentations of venous malformations: where and why? Pediatr Dermatol. 2013;30:534–540.
16. Hein KD, Mulliken JB, Kozakewich HP, Upton J, Burrows PE. Venous malformations of skeletal muscle. Plast Reconstr Surg. 2002;110:1625–1635.
17. Burrows PE, Mulliken JB, Fellows KE, Strand RD. Childhood hemangiomas and vascular malformations: angiographic differentiation. AJR Am J Roentgenol. 1983;141:483–488.
18. Hammer S, Uller W, Manger F, Fellner C, Zeman F, Wohlgemuth WA. Time-resolved magnetic resonance angiography (MRA) at 3.0 Tesla for evaluation of hemodynamic characteristics of vascular malformations: description of distinct subgroups. Eur Radiol. 2017;27:296–305.
19. Hammer S, Zeman F, Fellner C, Wohlgemuth WA, Uller W. Venous malformations: phleboliths correlate with the presence of arteriovenous microshunts. AJR Am J Roentgenol. 2018;211:1390–1396.
20. Patel AS, Schulman JM, Ruben BS, et al. Atypical MRI features in soft-tissue arteriovenous malformation: a novel imaging appearance with radiologic-pathologic correlation. Pediatr Radiol. 2015;45:1515–1521.
21. Uller W, Alomari AI, Richter GT. Arteriovenous malformations. Semin Pediatr Surg. 2014;23:203–207.
Keywords:

Contrast media; Hemodynamics; Magnetic resonance imaging; Vascular malformations

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Society for the Study of Vascular Anomalies.