Three-Dimensional Volumetric Analysis of Venous Malformations for Assessing the Effectiveness of Percutaneous Sclerotherapy

Yungying WANG,Hao GU,Li HU,Xi YANG,Hui CHEN ,Xiaoxi LIN

ABSTRACT BACKGROUND Percutaneous sclerotherapy can be used to successfully treat venous malformations (VMs) of the head,neck,and limbs.However,the standard curative effect of sclerotherapy has rarely been analyzed,and there is currently no accurate statistical method to measure the volume of VMs after sclerotherapy.Here,we propose a novel threedimensional (3D) reconstruction method to evaluate this effect.OBJECTIVE To test the feasibility of 3D software (MIMICS 19.0) to evaluate the treatment effect of sclerotherapy.METHODS This retrospective study included patients with VMs on the head,neck,and limbs who were treated with ethanol sclerotherapy or foam sclerotherapy every 8 weeks.MIMICS 19.0 was used to calculate the performance of the lesion after treatment and measure the VM volumes before and after the treatment.The effect of the clinical treatment dose on the lesion was evaluated,and the treatment effect of each patient was recorded.The relationship between the number of treatments and the reduced volume of VMs was analyzed.RESULTS Based on the MIMICS-calculated regions of interest (ROI),we found that 1 mL of ethanol reduced the lesion by 473 mm3 and that one dosage of foam (1 mL of polidocanol and 4 mL air content) reduced the lesion by 2 138 mm3,demonstrating that the foam sclerosing agent exhibited greater efficacy in this study.CONCLUSIONS The MIMICS 3D volume reconstruction method can effectively and safely evaluate the efficacy of sclerotherapy and provide a preoperative evaluation.This method is simple,accurate,and feasible.

KEY WORDS Venous malformations;Three-dimensional reconstruction;Digital imaging technology;Sclerotherapy

INTRODUCTION

Venous malformations (VMs) are a common type of vascular malformation that tend to be located in the head and neck regions or the extremities[1].On examination,VMs are compressible,non-pulsatile masses that usually exhibit a bluish tint on the overlying skin[2].VMs appear in childhood,tend to enlarge over time (especially during puberty and pregnancy due to hormonal effects),and do not regress;thus,these lesions may require treatment.In accordance with the clinical characteristics of the lesions of the vessel and the characteristics of the vascular endothelium,VMs are classified as vascular malformations,which have different characteristics from those of the original hemangioma.Due to insufficient venous development,the venous channel lacks smooth muscle cells and becomes dysfunctional.As venous blood stagnates,the venous sinus gradually expands,causing the shape to expand.In clinical manifestations,VMs are found in infants and children,where they usually appear as bluepurple plaques in the head and neck;these are common in the limbs and rare in the trunk.Their development speed is identical to their growth,they do not subside on their own,and they seriously affect the patient’s appearance.Therefore,patients who are concerned with their appearance tend to seek medical treatment[3].

Diagnosis of VMs is often performed using B-ultrasound or magnetic resonance imaging (MRI).B-ultrasound is an effective,simple method to detect VMs;it has high sensitivity and resolution for blood flow direction and tissue perfusion,which help to distinguish low flow.There is no significant correlation between the size,location,and depth of VMs and high-flow arteriovenous malformations.On computed tomography,only the adjacent bone tissue and calcification can be clearly distinguished.VMs can be divided into limited and nonlimited types,and the range of size of them can be clearly observed by MRI[4].To confirm the nature of the vascular malformation,an accurate diagnosis is required so that appropriate treatment can be planned.

At present,percutaneous sclerotherapy is the main treatment for VMs[5].In 2013,Qiu[6]reviewed 35 studies between 1986 and 2011 and confirmed that ethanol,polydoxol,ethanolamine oleate,sodium tetradecyl sulfate (STS),and other hardeners are effective for treating VMs,with a total efficiency of more than 90%.Common complications include damage to the skin,kidneys,nerves,and muscles.Moreover,the effectiveness achieved after each treatment is a concern for each patient.

Although studies have shown the effectiveness of percutaneous sclerotherapy,a clear research report demonstrating the treatment effect is lacking.In 2018,Asdahl[7]analyzed studies from March 2008 to October 2016 using data sources PubMed and EMBASE.In a randomized controlled trial and 44 cohort studies,the most common measurement methods for sclerotherapy included subjective measurements,objective measurements,MRI,and ultrasound imaging,and approximately 60% of the studies used multiple measurements.The literature published over the past decade lacks a clear method to assess the impact of sclerotherapy on VMs.Therefore,we recommend that a standard set of measurements should be defined.

In 2016,Alexander[8]reported a method using 3D volumetric analysis of lymphatic malformation to evaluate the therapeutic effect in 30 patients,but the efficiency of each treatment was not explicitly indicated by the results.Therefore,we used 3D volumetric analysis combined with MRI to calculate the effect of each treatment.

In this study,we reconstructed the volume measurement of VMs from T2-weighted (T2W) MRI data using MIMICS 19.0 software in order to test the feasibility of this 3D software for evaluating the treatment effect of sclerotherapy.

At a certain threshold,3D software can highlight the selected VM range by reconstruction of the VM volume data.VMs will show the characteristics of highlighting the selected VM range,the software calculated by the VMs of the 3D reconstruction volume data.The T2W images were analyzed before and after VM measurement,and the actual volume (cm3) of VM reduction was obtained.The method is much accurate measurement since it can select irregular boundaries and multiple lesions

MATERIAL AND METHODS

Patient Data and Lesion Selection

Patients who visited our center for the treatment of VMs in the head,neck,and limbs were recruited from March 2016 to May 2017.The included patients were either assigned to the ethanol treatment group or the foam treatment group.All patients underwent MRI before and after treatment.The experiment was set to an 8-week treatment interval to progress.

According to the VM classification reported by Stefan[9],the lesion was classified as an isolated malformation without peripheral drainage.The treatments were recorded for each patient.The clinical characteristics of the patients are listed in Table 1.

Treatment

Anhydrous ethanol is a potent percutaneous sclerotherapy agent that can rapidly damage vascular endothelial cells and form a large number of thrombi through the action of nearly“ablation”,thereby allowing fibrosis and occlusion of the lesion.Ceulen[10]concluded that 3% polidocanol foam was more effective than 1% polidocanol foam in 80 patients.The side effects were almost similar in both groups.Before treatment,the no.22-scalp needle cannula was cut to prevent blood from clotting in the longer scalp needle.After routine disinfection,the anatomicallocations of the VM lesions were identified by MRI.A 22-scalp needle was used percutaneously,directly,and blindly to reach the lesion.After reflux venous blood,the anesthetic agent (0.25% lidocaine) was injected,followed by a single dose of 1-14 mL ethanol.After injection,the pressure was maintained for 3-5 min to achieve absolute ethanol embolization of the VM lesions.

Table 1 Patient characteristics and clinical data

In the polidocanol foam group,a polyvinyl alcohol foam hardener was prepared according to Tessari’s technology production[11].A three-way tube was prepared using 5 mL of the syringe charge,4 mL of air,and polyglycol alcohol.Routine disinfection was performed.The location of the VM lesion was identified on MRI.The 22-scalp needle was directly blinded to the VM lesion.Following venous blood reflux,a single dose of 1 mL polyphenolate foam was injected.

MRI to 3D Reconstruction

Head and neck regions are frequent sites of VMs[12],and imaging plays a key role when surgical or interventional therapy is contemplated.MRI exhibits high sensitivity and specificity[13]and has the advantage of no ionizing radiation.For children with lesions near sensitive organs or patients with large lesions,MRI is the ideal examination method for clinical efficacy evaluation.MRI can provide both physiological and anatomical information.The patient was laid wearing a head collar facing the MRI scanner.The scan sequence included coronal T1-weighted imaging (T1WI),sagittal T2W imaging fat suppression,diffusion-weighted imaging,and dynamic enhanced scanning.The scan parameters were as follows:T1W image,single cross-section,and a layer thickness of 5 mm.MRI data were imported into analytical computers in the medical digital image and communication standard format Digital Imaging and Communications in Medicine (DICOM) 3.0,and the scanned images were transmitted to GE’s graphics workstations at a digital interface.

In MIMICS,there are two general methods for measuring VM volume.In the first method,the maximum diameter method,the lesion’s sagittal and cross-section of the three largest diameters are selected,and the multiplication is used to obtain the approximate volume of VMs.In the second method,the superposition method,the lesion images in each plane have a thickness of 5 mm.The irregular edge of the lesion is obtained with precise data according to the volume of each layer after the stack of VM volume.

According to the MR image,the difference between the different gray values of the ROI was classified into two types of pixels:the skin and gland bright signal and the fat black signal.Subsequently,the threshold of VM internal organization was determined and VMs were separated from the external background,which allowed us to obtain the lesion volume with high accuracy and practicability (Fig.1).In this study,method 2 was employed to calculate the volume difference before and after treatment in 16 patients.

The MIMICS l9.0 software was used to select the new project wizard.All T2W MR images of the patient were selected and imported into the software.The ROI 3D reconstruction imaging VM model was generated,and the range of VMs was selected under MIMICS 19.0.First,the 3D model was set to the cube area of the VMs,the image contrast was adjusted,the organization boundary of the different brightness of the region was cleared,and the appropriate threshold was set to complete the selection of VMs as a whole.Finally,3D calculation of all selected regions was performed,and the volume and 3D reconstruction model of VMs were obtained (Fig.2).

RESULTS

Volume Measurement

Fig.1 Lesion volume on DICOM

Fig.2 Indicator parameters of the lesion area in the MIMICS operation window

After ethanol treatment of the lesion (A),1 mL of ethanol reduced the lesion volume by 473 mm3.After treatment with foam sclerotherapy (B),1 dose of foam sclerotherapy (5 mL) reduced the volume by 2 138 mm3.The mean pre-treatment volumes were (A) 36 225.6 mm3and (B) 11 554.0 mm3;the mean post-treatment volumes were (A) 26 202.1 mm3and (B) 5 495.0 mm3;the total treatment volumes were (A) 169.5 mL and (B) 34 mL;the mean doses per mL of consumption were (A) 473 mm3and (B) 2 138 mm3;and the mean reduced volumes were (A) 10 023 mm3and (B) 6 339 mm3(Table 2).

All patients experienced a definitive effect after treatment (Fig.3).During the 1-year follow-up,there were no significant complications,and each patient was treated satisfactorily.

The Spearman rank correlation coefficient showed that there was a positive correlation between volume reduction and dose in the two groups.

Efficacy Evaluation

In the treatment using the intravascular sclerotherapyevaluation criteria,VMs were split into four levels as follows:level Ⅰ,0% to 25% (poor);level Ⅱ,26% to 50% (medium);level Ⅲ,51% to 75% (good);and level Ⅳ,76% to～100% (excellent).Levels Ⅲ and Ⅳ were added to evaluate efficiency.After this study,the degree of reduction in the volume of the lesion could be directly analyzed.The volume per treatment was fixed at 1 mL,and each time the volume reduction ratio was quantified.It was therefore concluded that the foam sclerosing agent was more effective in this study (Fig.4).

Table 2 Data statistics after treatment

Fig.3 Spearman correlations between volume reduction and dose between the groups

Typical Cases

In both groups of patients,the left masseter muscle had lesions,and the treatment efficiency of the two groups was compared.Typical case 1:A young man was injected with 5 mL of polidocanol foam sclerosing agent;the original size of the lesion was 29 301.88 mm3and was reduced to 8 812.59 mm3(Fig.5).Typical case 2:Aa young woman was injected with 15 mL of anhydrous ethanol hardener;the original size of the lesion was 5 139.28 mm3and was reduced to 2 772.39 mm3(Fig.6).Typical cases in both groups could be seen from a subjective perspective before and after treatment.

Fig.4 Rate of therapy of ethanol and polidocanol

DISCUSSION

Fig.5 MR images of a male patient undergoing 5 mL of polidocanol sclerotherapy

Fig.6 MR images of a female patient undergoing 15 mL of anhydrous ethanol sclerotherapy

Our results demonstrate that the MIMICS 3D volume reconstruction method is a simple,accurate,and feasible method to effectively and safely evaluate the efficacy of sclerotherapy and provide a preoperative evaluation.

VMs of the head and neck can be treated in several ways,including with percutaneous sclerotherapy.At present,there are no standardized parameters for initial lesion assessment or evaluation of treatment response.Over 60% of vascular malformations are VMs[14],and VM treatment is a major clinical challenge.VMs refer to low-velocity vascular malformations,based on the pathological anatomical characteristics of vascular malformations.The sclerotherapy of VMs has been adopted as the international standard for treatment.Anhydrous ethanol treatment of head and neck VMs has a positive effect,with a treatment efficiency of up to 74%[15].Polidocanol foam intravascular sclerotherapy,with mild pain during injection,is characterized by high efficiency,safety,fewer side effects,and a good cosmetic effect[16].Although surgical resection can be completely replaced in some lesions,multiple sclerotherapies are often required.Patients often look for treatments that provide satisfactory cosmetic results[17].However,there has been no evaluation standard for the sclerotherapy effect on VM.Most effects on malformation are evaluated using subjective measurements,objective measurements,planar MRI,and ultrasound imaging;however,there is no uniform forward-looking measurement.

In 2018,Gorman[18]studied 34 patients with VM treated with 3% STS (11%).The combination of ethanol and 3% STS versus ethanol alone showed a higher success rate (64% vs.60%).There was no significant relationship between the volume of sclerosant per lesion volume and the outcome.Combinations with ethanol were found to be the most effective sclerosing agents,whereas the hardening dose of the lesion volume did not affect the results.

The present study has some limitations.This study was a retrospective study,that is,a non-randomized controlled trial.For larger lesions,doctors prioritized absolute ethanol as treatment;as such,the study has a selection bias.Moreover,there was a human error in the current MRI gray value selected in the ROI by the MIMICS 19.0 software circle interactive medical image control system.Furthermore,this method requires patients to undergo MRI several times,and the cost of the inspection is more expensive and it is difficult to implement,whereas the general efficacy evaluation can lay a basis.Nonetheless,this method is feasible and can effectively and easily predict lesion variations in a 3D model.

CONCLUSION

VMs are a matter of concern in economically developing and densely populated areas.The 3D simulation method of this study will provide patients with a statistically significant treatment index.This method is straightforward and has become a standard effective treatment for patients.Subsequent studies should include larger sample sizes to explain several factors that may affect the choice of sclerosing agents and treatment outcomes.

ETHICS DECLARATIONS

Ethics Approval and Consent to Participate

This study received ethical approval from the Ethics Committee of the Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine.All participants provided written informed consent before study enrollment.

Consent for Publication

All the authors have consented to the publication of this article.

Competing Interests

The authors declare that they have no competing interests.The authors state that the views expressed in the article are their own and not the official position of the institution or funder.