Intravascular Ultrasound in the diagnosis and treatment of chronic cerebrospinal venous insufficiency



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Intravascular Ultrasound in the diagnosis and treatment of chronic cerebrospinal venous insufficiency

Salvatore J.A. Sclafani, MD, FSIR


American Access Care Physicians

Professor of Radiology, Surgery and Emergency Medicine

State University of New York Downstate Medical School

Brooklyn, New York


Introduction


Chronic Cerebrospinal venous insufficiency (CCSVI) is a clinical syndrome that results from outflow resistance of the veins that drain the brain and the spine. It presents with chronic fatigue and temperature intolerance, short term memory deficiencies and problems of concentration and executive processing, headaches, spasticity and vision deficiencies, among others (1-3). CCSVI is most commonly seen in patients with multiple sclerosis (4), but these symptoms have been reported in patients with jugular stenoses and occlusions caused by radical neck surgery, vascular access catheters, tumor compression, hypercoagulable states, and trauma and without antecedent cause. (5-8)

The primary venous conduits that constitute the cerebrospinal venous circuit include the right and left internal jugular vein (IJV), the right and left vertebral veins and the azygous vein. These are the major outflow veins of the brain and the spinal cord draining venous blood from the dural sinuses and from the vertebral plexus and spinal veins. There are also secondary outflow veins, namely the innominate veins and the superior vena cava. Augmentation of the primary outflow veins can result from obstruction of the "inflow" veins that are connected to the primary veins. These include the left renal vein that is connected to the hemiazygous vein and the left common iliac vein that is connected to the ascending lumbar vein.

The recommended diagnostic algorithm utilizes Doppler ultrasound of the deep cerebral veins, the IJVs and the vertebral veins in both the erect and supine positions to assess the hemodynamic consequences of outflow derangement and B-mode ultrasound to detect structural abnormalities. Doppler hemodynamic manifestations include reversal or absence of flow and loss of normal postural control in the erect position. A variety of B-mode abnormalities can be seen, including occlusions, stenoses and hypoplasias, thickened, elongated and immobile valves, septum and membranes. The detection of at least two of five criteria correlates highly with the presence of CCSVI. (9)

Magnetic resonance venography (MRV) and computed tomographic venography (CTV) have been used by some to screen for CCSVI. These examinations allow non-invasive visualization of the entirety of the veins of the neck, but in addition can detect stenoses, hypoplasias and occlusions of these veins. Moreover these imaging methods allow visualization of the central chest veins and the dural sinuses prior to venography. Additionally, some efforts have been made to quantify flow selectively in each of these critical veins.

Venography remains the Gold Standard for the visualization of the jugular veins, as well as of the azygous vein, a vein that cannot be imaged satisfactorily by MRV, CTV or Ultrasound. To its advantage, venography can also visualize the secondary veins, such as the left renal vein, the left common iliac vein and the ascending lumbar vein. Venography can also assess subjectively flow, stasis and reflux in these veins. To its advantage, the catheter study enables subsequent treatment by angioplasty of stenoses of these veins.

However, each of these imaging modalities has deficiencies that can negatively influence treatment decisions. Surface ultrasound cannot visualize well the confluens of the internal jugular vein and the subclavian vein because of the impediment of the clavicle. Angling the transducer into the chest may underestimate disease in this area. This is a critical deficiency because the area under the clavicle is the most common location for pathology in CCSVI. Similarly, the upper cervical jugular vein and the jugular bulb cannot be visualized by ultrasound because of the limited acoustical window resulting from the spine, mandible and skull. Moreover it is clear that ultrasound can evaluate completely neither the azygous vein nor the brachiocephalic veins. In addition assessing the degree of stenosis is unreliable by ultrasound.

MRV and CTV cannot evaluate intraluminal pathology, such as the immobile valves, webs, septations, membranes and duplications. As with ultrasound, they cannot evaluate satisfactorily the azygous and hemiazygous veins even though they are able to identify the compression syndromes of the renal vein and the iliac vein. Furthermore they often detect spurious stenoses that are not confirmed by venography. These stenoses may represent transient phasic narrowings or may result from diminished flow above true stenoses commonly located at the confluens region of the vein.

Similarly venography also has difficulties identifying the intraluminal pathology because density of the injected contrast may obscure these findings. Moreover venographic determination of the size of the veins is rather subjective and may mislead without multiple projections that would be necessary to assess this characteristic. The IJV is often not a circular object; rather it is oval or complex in shape. Thus determination of the diameter of the vein if often arbitrary and often underestimates or underestimates the proper size of balloon for angioplasty. In light of the high pressures necessary to disrupt this internal pathological stenosis, proper sizing is crucial to avoidance of injury to the vein by overdilatation or early recurrent stenosis by underdilatation.

All of the luminographic studies, such as venography, MRV and CTV, suffer from their "snapshot" nature. Outflow obstruction of the jugular veins results in slow flow or stasis. Because there is an alternative cerebral outflow via the vertebral veins, decompression results in diminished IJV volume these thin walled IJVs that can collapse against rigid structures such as the spine, the carotid artery and neck musculature. Accurate depiction of these veins requires multiple views, such as imaging during inspiration and expiration, during flexion and extension, and during rotations of the neck. These maneuvers cannot be done in real time by MRV and CTV and doing them during venography is time-consuming to the operator and results in increased radiation dose to the patient.

Intravascular Ultrasound


Intravascular ultrasound provides benefits that can address many of the deficiencies of venography, surface Duplex examination, CTV and MRV. The most common indications for intravascular ultrasound have been in the evaluation and treatment of arterial disease, notably in the management of coronary artery disease. Its ability to differentiate various tissue characteristics enables one to assess plaque morphology, detect lipid and calcium deposits and elaborate the degree and distribution of calcification within atherosclerotic plaques. It can thus help evaluate the vulnerable soft, un-ruptured plaque. IVUS is useful in characterization of both the vessel wall and the endothelium. It can assess mural and endothelial thickness and clarify whether narrowings are the result of intimal or mural disease.

IVUS has been shown to provide a more accurate assessment of vessel circumference and cross sectional area and thus is useful in detecting critical stenoses. Such elegant analysis of the dimensions of the vessel allows a more accurate selection of balloon size, thus reducing risk of injury and providing more effective angioplasty. IVUS allows improved visualization of intimal thickening after angioplasty. Moreover, IVUS enables the operator to see how well apposed stents are to the intima and thus guides the need for additional angioplasty to reduce separation between intima and stent. This may facilitate endothelialization of the stent.

Although the vast majority of publications on IVUS relate to the coronary arteries, authors have reported on the value of IVUS in many other conditions, both within arteries and veins. (10)

More recently, benefits have been reported in a number of peripheral arterial applications. Some of the same advantages of IVUS have been exploited in the treatment of peripheral atherosclerotic disease (11). Plaque morphology, more accurate determination of vessel size and degree of stenosis, and tissue characterization by IVUS have been added to the information from angioplasty and thus facilitating and enhancing atherectomy and stenting of peripheral, renal and carotid atherosclerosis. (12)

Authors have also been enthusiastic about using IVUS in the deployment of aortic endographs. More accurate measurement of vessel circumference and the sonographic visualization of the location of aortic branches have allowed greater precision in determining both upper and lower landing zones. The addition of IVUS can alter the plans derived by CTA, contradicting CT’s determination that endovascular stenting was either feasible or futile.

IVUS has been shown to facilitate the diagnosis of aortic dissection. It is highly effective in detecting entry points along the dissected aorta. This can facilitate placement of stents and reduce need for operative intervention. Moreover, IVUS has been shown to be an effective guidance method during fenestration procedures. (13-15)

The use of IVUS in cases of traumatic aortic injury has been shown to improve diagnosis, especially in patients with equivocal aortography, by allowing differentiation of ductus diverticulum and pseudoaneurysm. Indeed, it was shown to be superior to aortography in one series of fourteen patients with a sensitivity of 92% and a specificity of 100%. (16)

While much less commonly reported than use in arterial disease, IVUS has shown merit in a variety of venous pathologies and treatments. Because of its portability, IVUS as a guidance method has been recommended for placement of inferior vena caval filters. The ability to precisely determine the circumference of the caval lumen and to localize all renal vein tributaries without contrast media or ionizing radiation has advantages. Filters can be deployed in an intensive care unit, thus avoiding risks of transport of critically ill patients. The ability to perform the procedure without the use of iodinated contrast media is such patients is a distinct advantage.

The use of IVUS for venous disease in patients with renal insufficiency or in patients with potentially life threatening allergies to contrast media has also been reported in management of dialysis grafts and fistulae, and central venous stenosis. (17-18)

Negen and Raju have argued effectively for the use of IVUS in patients with venous disease, notably in chronic iliac vein stenosis and occlusions. They point to the fact that hemodynamic data so helpful in arterial obstructions is often limited or equivocal in venous disease because of small differences. The significance of pull-through pressure gradients is difficult to interpret. Small degrees of pressure differential may indeed be significant, given the large volumes and high compliance. Rather morphological area stenosis of 50% seems to provide some predictive value of clinical improvement after angioplasty. They recognize the rather irregular shape of the iliac vein and the difficulties in using single view diameters to make stenosis measurements. Further they point out that intraluminal abnormalities, such as immobile valves, subintimal edema, and echogenic material, probably representing trabeculae, septa, and webs, cannot be seen by venography which obscures them with dense contrast media. (19-21)

To date I can find nothing in the literature that describes the IVUS findings of CCSVI, nor one that reports on abnormalities of the internal jugular vein and the azygous vein in CCSVI or other diseases.

Technical considerations


Intravascular ultrasound is a technique that places within a hollow structure, such as a vein or artery, a catheter or a wire containing a miniaturized phased array ultrasonic transducer that sends out frequencies of 10 to 50 megahertz and then captures reflections off near objects. The catheter or wire is 3.2-8.2 French in diameter and is attached externally to a cart that performs the reformations and calculations. The systems are also equipped with a motorized unit that can retract the catheter at a fixed rate. The device can be introduced through a sheath of 6-9 Fr diameters and advanced over a 0.01inch-0.038 inch guidewire by either over the wire or rapid exchange techniques. (11)

Images that are created are cross sectional B-mode images with resolution of 110-150 microns and penetration of about 20 millimeters. In addition to cross sectional images, modern units can create longitudinal reformations that some believe provide images that are more revealing views of length of stenosis and degree of narrowing. However, this requires use of a motorized catheter driver. Some vendors have now made available wires that can capture hemodynamic data such as Doppler flow rates, pressures and gradients. Assessment of stenotic and microvascular resistance is now possible, although the utility of this information in CCSVI is not established.

Other methodologies include ChromaFlo and VH (Virtual Histology). Chromaflow detects blood flow and represents it on imaging with a red color. Thus this non-quantifiable presentation of flow aids in differentiating tissue types that are similar to flowing blood on the B-mode images.  VH-IVUS is a spectrum analysis of IVUS-derived radiofrequency (RF) data acquired at the top of the R wave. It allows reconstruction of a color coded map showing a more detailed analysis of plaque composition and morphology. It is suggested that VH-IVUS has the ability to detect lesions that predict high risk lesions in coronary artery disease. It is possible that such manipulations may distinguish various tissue types in CCSVI and may be able to predict response to angioplasty. However this feature does not yet exist.

Finally, IVUS presents a real-time cross sectional view. During that interrogation it is possible to analyze various questionable areas of the venous anatomy while performing a variety of physiological maneuvers such as Valsalva and reverse Valsalva, inspiration and expiration, flexion and extension and varying degrees of rotation. We shall see that there is great advantage to such maneuvers in the evaluation of CCSVI.


Justification for IVUS in CCSVI


IVUS is indicated as a primary evaluation of intraluminal venous pathology, as a tool for stenosis analysis, as a method of detecting pressure gradients, as an aid for assessing inconstant or atypical narrowings and as a post-angioplasty exam. In unusual circumstances, IVUS can allow the procedure without use of iodinated contrast media in patients who have had potentially life-threatening allergic reactions to contrast media or who have severe renal insufficiency but do not yet require chronic hemodialysis. IVUS can provide sufficient information to perform this procedure without venography although venography does make this procedure easier.

A recent presentation of a joint meeting of the European Committee on Research in MS (ECTRIMS) and the American Committee on Research in MS (ACTRIMS) reported on a comparison of jugular venous pathology from specimens obtained at autopsy from cadavers of patients with multiple sclerosis and of people who died of unrelated illness. (22) The authors discovered that stenoses were common in both group. What distinguished the MS group from the non-MS group was a preponderance of intraluminal lesions, such as immobile or inverted valves and other valvular deformities, septum, webs, membranes and duplications. This is consistent with the theory that CCSVI is the result of malformation of the maturation of the fetal cardinal system of cerebrospinal veins into the adult system (23).

The preponderance of intraluminal lesions suggests that an intraluminal study is appropriate for the complete diagnosis of this pathology. Venography can demonstrate the major stenotic lesions. However superimposition of valvular cusps and reflux opacification of the vessel distal to a stenosis may obscure them. Moreover, venography cannot distinguish the various etiologies of such stenoses. Strictures, hypoplasia, and valvular stenosis can look identical on venography which provides a simple lumenogram. Endoluminal studies are superior to contrast studies that obscure such pathology by the necessary density of the contrast media. Negen and Raju have shown evidence that such venous pathology in the iliac vein is unrecognized by venography and yet well seen by IVUS. (21)

IVUS is also valuable in evaluating transient narrowings that are not fixed and may be physiological. Moreover veins often have irregular circumference; compressed by surrounding muscles, arteries and bones they may take varied and unusual contours that make it difficult to determine their diameter. As such, stenosis analysis may be extraordinarily difficult and inaccurate. Simple diameter measurements rarely provide a good maker of stenosis. Nor are such diameter measurements sufficient to choose an appropriate balloon size for angioplasty. Finally IVUS provides an excellent methodology of evaluating the effectiveness of venoplasty and valvuloplasty. The elimination of immobile valves is particularly well seen on IVUS. Complications of angioplasty are also better visualized by IVUS. Thrombus and dissections are readily seen on IVUS.


Performing the examination


I perform diagnosis and treatment of CCSVI using fluoroscopy, venography, intravascular ultrasound and external ultrasound access guidance. The procedure is performed under local anesthesia and with micropuncture access. Vascular entry is obtained under external ultrasound guidance through a left inguinal approach, to enter the saphenous vein at the saphenofemoral junction. A 10 French sheath is introduced and positioned above the right atrium in the superior vena cava. The sheath is positioned and all instrumentation is moved through the sheath, as an essential protection because the very small wire required to track the IVUS buckles into the heart and mat cause arrhythmias.

Once the sheath is in place, all, or at least most, of the catheterizations are performed over the 0.014 inch guidewire needed for the IVUS. I perform venography followed by IVUS for each of the three major cerebrospinal outflow veins, namely the right and left IJV and the azygous vein. I perform venography alone in the majority of transverse sinuses, in the left renal vein, in the left common and external iliac vein and in the left ascending lumbar vein. I do not recommend routine IVUS of the left renal vein or the left iliac vein because these veins are rarely associated with immobile valves. However when stenoses or prominent collaterals are identified, IVUS is used. When compression of the renal or iliac veins is seen, the diagnosis of Nutcracker or May Thurner syndrome can be made. IVUS is then critical to accurate sizing of these veins to reduce risk of migration.

With the guidewire in the transverse sinus and using a rapid exchange system, the IVUS is positioned in the jugular bulb and then withdrawn manually at deliberate speed down into the innominate vein. I do not use the automated pull-back device because such devices were developed for coronary use and the pull back moves too slowly to be practical for the long length of the jugular vein. Critical areas to evaluate include the upper internal jugular vein at the C-2 level, the mid jugular vein where venous compression by the carotid artery or the strap muscles occurs and, most importantly in the lower jugular vein at the confluens with the subclavian vein where most of the pathology is located. (Figure 1)

After azygous venography IVUS is performed throughout the azygous vein, extending as far down the azygous and hemiazygous as possible. Transient narrowings are common in the azygous. Inspection of narrowings throughout the ascending azygous should include inspiration and expiration views as this area common dilates during inspiration. I do not treat transient narrowings. The area of the junction of the ascending azygous and its arch is inspected in great detail. Subtle immobile valves in the azygous vein are often unrecognizable on venography and are often visualized only by IVUS. (Figure 2)

B-mode imaging in both the cross sectional and longitudinal views are important. The cross-section image looks at the circumference of the vein, and reflective tissue such as webs, membranes, septums and valves. The longitudinal view gives a good view of collateral entries, longitudinal views of stenoses and a different view of intraluminal pathology. I have not relied upon ChromaFlo or Virtual Histology at this time.

Diagnostic IVUS: findings

Normal Internal Jugular vein (Figure 1)


The IJVs are the primary venous outlets for the cerebral blood volume when a human is supine. The vertebral veins and the vertebral plexus assume this function in the erect position. The sigmoid sinus, the terminal component of the transverse sinus, combines with the inferior petrosal sinus to form the superior jugular bulb. The vein runs a continuous course down the neck in the lateral aspect of the carotid sheath where it dilates (inferior bulb) before enter the innominate vein at its confluens with the subclavian vein. Valves, usually biscuspid, are located near the confluens are present in about 85% of humans and. There may be more than one set of valves. Major branches of the IJV include the inferior petrosal sinus, pharyngeal vein, the common facial vein, the lingual vein, and superior and middle thyroid veins. In CCSVI IJV outflow is compromised

On IVUS, the IJV varies in its appearance depending upon location in the neck. The upper segment (J3) starts as a larger structure (superior jugular bulb) that quickly diminishes in circumference. It occasionally flattens as it courses over the second cervical vertebra before expanding in diameter in the mid portion of the neck (J2). Often tributaries are seen in this region. A second crescentic indentation, representing the compression by the carotid artery, may be seen in this region. The lower jugular vein is normally dilated as it joins the subclavian vein (inferior bulb).


Normal Azygous venous system (Figure 2)


The azygous vein is a critical conduit that drains the thoracic and, to some degree, the lumbar spinal venous circulation. The central and radial spinal veins, draining via vertebral plexuses and anterior and posterior medullary veins ultimately form intervertebral veins that connect with intercostal veins before draining into the azygous and hemiazygous veins. These spinal veins and plexuses are connected directly to the venous drainage of the brainstem and the cervical and lumbar spinal cord, via anterior and posterior medial spinal veins and dural plexuses.

The azygous vein is a continuation of the right ascending lumbar vein; the hemiazygous vein is a continuation of the left ascending lumbar vein or a branch of the left renal vein. The accessory hemiazygous vein is a continuation of the upper left intercostal veins and may drain into the left innominate vein or into the azygous vein. Valves are typically present in the arch of the azygous vein; they may be multiple.

On IVUS the azygous vein is usually a rounded structure with little sonolucency in the wall as all veins have minimal muscularis. At the level of the aorta, the vein may be flattened or narrowed. One sees segmental veins entering it; segmental arteries are posterior to the vein and may temporarily indent the vein. At the junction of the ascending azygous vein with the arch of the azygous, a large draining vein may enter it. This is the continuation of the accessory hemiazygous vein. Valves are usually present within the arch of the azygous vein. When thickened they are visible, echogenic and show limited motion.

Abnormal


Venography provides a comprehensive technique for detection of stenoses of the major cerebrospinal veins. These stenoses are usually well seen on contrast studies. However, the nature of such stenoses may be less clear. IVUS provides important data regarding the nature of stenoses: the anatomic nature of stenoses, the phasic nature of stenoses and whether they are intrinsic or extrinsic in nature.

Assessment of all valvular structures is very important as the majority of abnormalities are located in areas of valves and most abnormalities are malformations of valves. Intraluminal bright signals can be misinterpreted as artifacts but they should be considered very carefully. Moving the transducer and then returning to the same area looking for the persistent bright reflections in the same location is a helpful tool in eliminating artifacts from serious consideration. The examination is reviewed both in cross sectional view and in the longitudinal mode.


Valves (Figure 3)


Normal valves are almost imperceptible: gossamer structures that are not easily visible. Abnormal valves are more easily seen. They are characterized by irregular thickening, poor mobility and bulging cusps. Thickening may be small foci of echogenic spots measuring less than a millimeter or longer areas of thickening. These are highly echogenic. These thickened areas may form a circular or oval circumference. The circumference may progressively decrease as the transducer is moved down the vein toward the chest. The valve appears to sway to and fro. One sees that the edges of these valves move little and never extend to the lateral walls of the vein. Uncommonly the valve may be seen en face at one level. On the longitudinal view, the lumen may be narrow and there may be two parallel signals (the “double echo" sign) that represent echoes off the valve and off the outer wall of the vein.

Septum (Figure 4)


Septums are seen as thin vertical bands extending up and down the vein. They may be thin or have areas of patchy echogenicity similar to the leaflets of valves. They may be compared to elongated valve leaflets. One can sometimes follow these bands to their attachment to the wall proximally or distally, forming a sort of "windsock". Some septum form a blind ending sack dividing the vein into two separate chambers, only one of which is in continuity with the cephalad lumen, analogous to a dissection. The "false" lumen may bulge and compress the "true" lumen on Valsalva maneuver. Septum may also show thickening and increased echogenicity, similar to abnormal valves. Differentiation relies upon the absence of an opposing valve leaflet. The septum appears to be taut against the IVUS probe.

Membrane (Figure 5)


A membrane is a horizontal band of tissue, like a valve that extends transversely across the vein as well. On the longitudinal view, septum shows as relatively thin lines of tissue running parallel to the venous wall. They may be very difficult to visualize on IVUS because of their horizontal nature.

Web (Figure 6)


Webs are bands of tissue remaining within the lumen of the vein. They are thought to be sequellae of the de-differentiation/re-differentiation of the veins during the transition from the fetal cardinal system into the adult system. Webs are another abnormality that is often not recognizable by venography because of its location within the lumen. Webs are represented as echogenic material within the vein lumen that is persistent and located in the same location during several interrogations with the IVUS probe. They are most commonly seen within the azygous vein and less commonly in the jugular system. On longitudinal view they are usually seen as random areas of high echogenicity.

Thrombus (Figure 7)


Thrombus is another echogenic material within the lumen. Clot tends to be thicker and amorphous and has a speckled and more brightly echogenic character. It is also inconstant in location and less reproducible.

Diffuse narrowings


Intravascular ultrasound is very useful in assessing and differentiating the many causes of long narrowed segments Diffuse luminal narrowing can be a phasic, inconstant phenomenon or it can be caused by compression syndromes, by hypoplasia, by intimal hyperplasia or by post-thrombotic recanalization. Each of these presents venographically as a narrow contrast column. Differentiating these problems is sometimes challenging but important as different treatment strategies are warranted. Treatments vary from doing nothing to stenting.

Inconstant narrowing (Figure 8)


Inconstant narrowings are a physiological effect frequently associated with fixed stenoses that are located more centrally in the vein. The dual outflow system of the cerebral venous system through the internal jugular veins and the vertebral veins and vertebral plexus allows the obstructed vein to decompress. Because of the compliance of the veins, the vein can collapse. Such collapse may be more pronounced due to pressure upon this vein by the internal or common carotid artery or compressed by muscles.

Venography, as a static sequence, does not allow dynamic imaging because of time constraints and radiation exposure. Imaging with IVUS is free from these impediments and allows one to place the transducer at the point of interest and perform a variety of maneuvers. Maneuvers that increase flow by activation of the thoracic pump, such as deep expiration, may increase flow through the vein. Changing neck position, such as flexion and extension, internal or external rotation may reduce flow by increasing the pressure on the IJV.

Other compressions are more significant and IVUS can plan an important role in their evaluation. The Nutcracker and the May-Thurner syndrome are clinically manifested obstruction of the left renal vein and left common iliac vein that are caused by compression of these veins between two structures. IVUS shows complete flattening of the vein, associated with a prominent hemiazygous, or renal vein or, is

Long luminal narrowings (Figure 9 )


Long luminal narrowings may be caused by hypoplasia, intimal hyperplasia, post-thrombotic recanalization, or perivenous inflammatory processes. Venographic appearance of these entities can be virtually indistinguishable. When the luminal diameter is completely collapsed, differentiation of these abnormalities can be impossible. While IVUS may have theoretical advantages over venography in evaluating some of these conditions, there is little data published in the literature on this subject in general and none as it relates to CCSVI or jugular veins.

However, IVUS has the potential to differentiate these problems, based upon the echogenicity of the offending pathology. Hypoplasia shows a narrow lumen but the echogenicity of the wall may be normal. In a recanalized vessel, IVUS may show intraluminal thrombus lining the interior of the vein. Thrombus is highly echogenic and often can be differentiated from the reflections of the wall itself. The echogenic areas may be interspersed with areas of diminished echogenicity. Echogenicity will be less for intimal hyperplasia than for thrombus lining the vessel wall. Perivenous inflammation may be detectable as separate from the vein itself.


Use of IVUS for balloon selection (Table 1, Figure 10)


Balloon sizing is a great challenge in treating stenoses of the internal jugular veins. Unlike the azygous vein and arteries which have a relatively uniform circular shape, the internal jugular veins do not. They may have a round, oval or multifaceted shape. Venography cannot accurately detect these shapes without the use of multiple views. Moreover, maximum and minimum diameters may be so disparate that simple estimates may grossly underestimate or overestimate the balloon size selection. Because these stenoses usually require large balloons and high pressures, improper sizing may result in serious complications such as dissection, tears and occlusions or inadequate distension and ineffective treatment.

Analysis by IVUS makes quite clear the deficiencies of venography. The cross sectional anatomy of the vein and the variation of size based on phase of respiration may it clear that cross sectional area (circumference) is the superior criteria for assessing size of the vein and for selecting the appropriate balloon for venoplasty or valvuloplasty.


Post intervention assessment


IVUS is helpful in monitoring the treatment. Because many of the intraluminal pathological states are only clearly detectable by IVUS, assessment of the post-angioplasty state is best done by IVUS. Incomplete opening of immobile valves and incomplete disruptions of webs and septum are readily detected by IVUS.

The major complications of treatment of CCSVI are procedural injuries such as lacerations, valvular avulsions, and dissections. They may be difficult to differentiate on venography alone but are easily differentiated on IVUS. Further post-procedural stenosis caused by intimal hyperplasia and in-stent stenosis can be detected and quantified.



Summary

Intravascular ultrasound is an essential imaging modality that facilitates detection of the intraluminal pathology associated with CCSVI, including valve abnormalities, webs and septum. It facilitates differentiation of a variety of stenotic lesions. IVUS allows precision in sizing angioplasty balloons and is an excellent method of judging treatment results and complications. It should be considered part of the standard of care.


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Captions for illustrations

Figure 1. Normal internal jugular IVUS


IVUS from the transverse sinus (A) to the confluens with the subclavian vein (B). Note compression of the carotid artery of the J2 segment of the IJV (F).

Index: 1. Transverse sinus tributary, possibly posterior cerebral vein or condylar emissary vein. 2. Inferior petrosal vein entering sigmoid sinus; 3. Pharyngeal veins in upper IJV; 4. Facial vein; 5. Superior thyroid veins; 6. Inferior thyroid veins; 7. Confluens of IJV with subclavian vein.


Figure 2: Normal azygous IVUS


IVUS of the azygous vein IVUS from distal ascending portion (A) to junction of the arch with the superior vena cava (F)

Legend: 1. intercostal artery (asterisk) indenting the azygous vein, 2. Intercostal vein; 3. Typical compression of mid-portion of the ascending azygous vein; 4. Spine; 5. Aorta; 6.orifice of accessory hemiazygous vein.


Figure 3: Valvular stenosis


Figure 3A: Partial valvular stenosis with associated webs: 1. shows 60% stenosis of the IJV at the confluens with the subclavian vein. Contast contour is smooth. 2. The IVUS probe at site of interrogation. 3. There is evidence of echogenic thickening at the edges of this immobile valve (white arrows). This represents the stenosis. The outer wall of the vein (black arrows) is much larger than the area that contains the contrast media

Figure 3B: Total valvular obstruction: 1. Axial and longitudinal views show a widely patent upper internal jugular vein. There is strong lumen/intimal interface. 2. More inferiorly as the transducer traverses the obstruction, a lumen is not visible on either longitudinal or axial views.


Figure 4 Septum


Figure 4A: Internal jugular septum: 1. Arrows point to a subtle "jet" of contrast at the confluens. This stenosis was missed by the first angiographer. 2. Axial IVUS shows the septum extending down to the innominate vein confluens (arrows). 3. Longitudinal IVUS reveals the septum dividing the lumen (arrowheads). 4. Angioplasty reveals the area of stenosis. High pressures were required to relieve this stenosis.

Figure 4B: Occult Azygous septum: 1.Venography was interpreted as being normal, even in retrospect. Arrow points to the area of abnormality seen on IVUS. 2. Axial IVUS shows intraluminal echogenic tissue (arrows). 3. Longitudinal IVUS clearly demonstrates the intraluminal tissue.


Figure 5: Membrane.


Membranes are transverse flaps that obstruct flow. They likely represent malformed valve tissue. Venography (A) with the catheter cephalad to the membrane appears normal. With the catheter withdrawn centrally (B), the membrane becomes visible (arrows). It is postulated that the catheter has pushed the membrane open against the lateral wall in Figure 7A.

Figure 6: Web in Azygous:


Webs are small tangles of tissue within the lumen of the vein possibly remnants of the cardinal vein maturation into the adult veins. 1. Arrows point to small areas of echogenic material. They may represent webs. However single areas of abnormal thickening of a valve could cause such an appearance. 2. The longitudinal view illustrates that this tissue has the random nature of a web (white circle) rather than of a valve.

Figure 7: Thrombus in dural sinus and IJV:


A. Thrombus fills the lumen and surrounds the transducer (curved arrow) which nearly fills the lumen. The thrombus is displayed as bright mottled echogenic reflections. The venous wall is well seen (straight arrow); in this case it is located within the dural sinus characterized by a triangular shape. B.The brightly echogenic thrombus extends into the internal jugular vein.

Figure 8: Phasic narrowing of azygous vein


Venography (not shown) revealed a long tapered narrowing of the ascending part of the azygous vein. IVUS, performed in both expiration and inspiration, clearly shows the phasic nature of this stenosis. No benefit will be derived from venoplasty because IVUS has demonstrated that this is not a fixed stenosis.

Figure 9: Intimal hyperplasia


Figure 9A: Intimal hyperplasia after thrombosis recanalization: 1. It is difficult to see the stenosis on this axial image because of the lack of echogenicity of the cause. 2. The longitudinal view shows this to great advantage. Arrows point to the edge of intimal which is markedly thickened.

Figure 9B: Intimal Hyperplasia within stent: 1. Venography shows occlusion of a stent placed during treatment of CCSVI by another physician. Differentiation of thrombus and intimal hyperplasia cannot be discerned. 2. After first attempt of suction aspiration, axial IVUS differentiates echogenic stent (black arrow) from echolucent intimal hyperplasia (white arrow) from echogenic thrombus (dotted arrow).


Figure 10: Using IVUS for treatment planning


Figure 10A: Assessing vein size before angioplasty: This axial IVUS illustrates some of the difficulty in assessing dimensions of veins and in choosing the proper balloon for safe and effective treatment of stenoses. Depending on orientations of the central ray of the fluoroscope and the vein axis, widely discrepant estimations of size may occur. The shortest diameter is less that 6 millimeters and the longest diameter is greater than 11 millimeters. Too small a balloon may be ineffective or result in short term clinical response. Too large a balloon may overdistend and injure the vein, thus increasing risk of stenosis or tear of the vein wall. Seeking a balloon 50% greater in size than this vein would indicate a balloon with CSA of about 100 mm2. A ...mm balloon was chosen.

Figure 10B: Quantifying stenosis: 1. Venography illustrates overdilation of the IJV during procedure done by a prior proceduralist. This stenosis was mostly likely caused by angioplasty of the incorrect segment or restenosis. 2. Curved echo represents wall of stenosed valves without remainder of vein excluded from direct flow. 3. Cross sectional measurement of both inner stenotic lumen and outer edge of wall, allows accurate calculation of percentage stenosis of 61.7% as opposed to values derived from diameter measurements ranging from 13% to 52%.



Table 1 Angioplasty balloon cross sectional area

Balloon Diameter (mm)

CSA (mm2)




Balloon Diameter (mm)

CSA (mm2)

5

2




12

113

6

28




14

154

7

38




16

201

8

50




18

254

9

63




20

314

10

79




22

380

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