Imaging of Hereditary Hemorrhagic Telangiectasia

PAVM is the most frequent lesion of the lung in patients with HHT. It occurs in 20% to 50% and provokes different clinical symptoms, such as dyspnea, cyanosis, massive hemoptysis, and hemothorax [1]. The shunt induces various paradoxical emboli such as cruoric, bacterial, and gaseous [1]. Currently, it is known that for clinical relevance, the diameter of the artery of the PAVM must be ≥3 mm. However, one case with a feeding artery diameter <3 mm (Fig. 1) and responsible for ischemic stroke has been reported [3].

The anatomic structure of the PAVM is classified according to the two types [4] defined as simple, with a single artery feeding into an aneurysmal communication with a single draining vein (Fig. 2, Movies 1 and 2), and complex, with two or more arterial branches communicating via an aneurysm with two or more draining veins (Fig. 3). On chest X-ray, a PAVM classically appears as a well-defined nodule with a minimum of two branching vessels (Fig. 4A). However, chest X-ray, although rather specific, is not sensitive [5]. Diagnosis is performed on unenhanced helical CT with a small slab of maximum intensity projection reconstruction showing one or more enlarged arteries, feeding a serpiginous mass or nodule, and one or more draining veins (Fig. 4B and C) [5]. Contrast-enhanced magnetic resonance angiography (CE-MRA) shows clearly all PAVMs (Fig. 4D) whose feeding arteries are larger than 3 mm [6]. Because PAVMs have predilections for affecting the lower lobes, exploration of the pleural sac is fundamental (Fig. 5A). Pulmonary angiography, which is an invasive procedure, less effective than chest CT, is no longer used for diagnostic purposes and its use is restricted to treatment. Transarterial PAVM vaso-occlusion with coils (Fig. 5B and C) is currently the treatment of choice [1]. Because of possible reperfusion more than the development of small PAVMs due to redistribution of the hemodynamic flow after transcatheter occlusion of large PAVMs, a CT or CE-MRA follow-up (Fig. 6A and B) is recommended [6]. Reperfusion of occluded PAVMs occurs in as many as 19% [7] of them after initially successful treatment (Fig. 7A); the flux through the coils is better seen on CE-MRA (Fig. 7B) and is confirmed during the new vaso-occlusion procedure (Fig. 7C). Reperfusion risk increases with increasing PAVM feeding artery diameter, the use of a small number of coils (one or two) [8] (Fig. 8) or oversized coils, and coil placement proximally within the feeding artery. When reperfusion appears, the patient remains at risk for complications, so a new embolization must be performed [9]. When the cause is too proximal coil placement, the reperfusion can be due to a hypertrophy of a bronchial or systemic artery [10]; such a reperfusion does not cause shunting but can be responsible for hemoptysis.

The mechanisms of central nervous system (CNS) involvement in HHT are distal emboli, cerebrovascular malformation (CVM), and metabolic disorders [2, 11]. PAVM shunting that avoids the filtering effect of pulmonary capillaries is the most frequent mechanism inducing cerebral embolism and subsequent stroke (Fig. 9) or brain abscess secondary to cruoric and septic emboli, respectively (Fig. 10A). Furthermore, polycythemia secondary to chronic hypoxemia favors in situ formation of a cruoric embolus [1]. Multiple ischemic strokes in different arterial territories at different ages characterize the embolic mechanism in HHT (Fig. 9). Brain abscess is the most serious neurologic complication, occurring in 5% to 10% of patients with PAVM. Typically in HHT these abscesses are multiple and recurrent, affecting the superficial layers of the cerebral lobes (mostly the parietal lobe) and developing often between the third and the fifth decade of life, when PAVMs increase in size and number. Transarterial PAVM vaso-occlusion is a key procedure to prevent these cerebral complications in HHT.

Spinal and cerebral vascular malformations are manifestations of underlying vascular dysplasia [12]. These lesions represent abnormal arteriovenous connections that failed to differentiate properly into arteriolar, capillary, and venular channels [13]. On magnetic resonance imaging (MRI), CVMs appear as areas of serpiginous flow voids insinuating into the brain parenchyma (Fig. 11). Patients with HHT often have multiple malformations of various types, some of them with an atypical or indeterminate MRI appearance [14]. Cerebral angiography may be required for diagnosis of equivocal lesions and for planning of treatment. The therapy for symptomatic CVMs is surgical resection, stereotactic radiosurgery, embolization, or a combination of these treatments [15].

Finally, the T1-weighted image hyperintensity of the basal nuclei correlates with a metabolic disorder related to hepatic portal vein shunt [16].

Hepatic involvement occurs in 30% to 73% of patients with HHT; most of them are asymptomatic or have a slight elevation of γ-glutamyltransferase (GGT) but rare complications occur, especially in female patients [11, 17].

Three different and often concurrent types of intrahepatic shunts (hepatic artery to hepatic veins, hepatic artery to portal vein, and portal vein to hepatic veins) are responsible for the parenchymal, vascular, and bile duct signs [11]. Hepatic abnormalities are diagnosed by Doppler ultrasound, MDCT, MRI, and MRA. Hepatic ultrasound associated with Doppler is a good tool with an experienced investigator [18]; otherwise findings can be considered as normal in the early stage because telangiectases are difficult to diagnose. The diameter of the common hepatic artery (>7 mm; Fig. 12A) and intrahepatic hypervascularization are suitable sonographic diagnostic parameters of HHT with a high sensitivity and specificity [18]. Rarely, Doppler ultrasound can reveal pulsatile portal flow (arterioportal shunt; Fig. 12B) or pulsatile hepatic vein flow (arteriovenous shunt; Fig. 12C).

Hepatic vascular lesions on MDCT range from tiny telangiectases (Fig. 12D) to transient perfusion abnormalities and large confluent focal vascular masses [19]. These lesions are often associated with arteriovenous, arterioportal, or portovenous shunts and hepatic artery enlargement (Fig. 12E–G). Telengiectases are hypervascular rounded nodules (varying from a few millimeters to 1 cm in size) localized in a subcapsular position in the arterial and late arterial phases, often becoming isointense with the hepatic parenchyma in the hepatic parenchymal phase. Arteriography, too aggressive for a screening and diagnosis tool, could be the best method to characterize telangiectases.

The natural evolution of hepatic teangiectasia in MRO patients is toward intrahepatic vascular shunts [20]. If simple telangiectasis can rarely provoke a painful liver with a slight elevation of GGT, arteriovenous shunts are more communicative. An arterioportal shunt may rarely induce portal hypertension, ascites, encephalopathy, and hematemesis. An arteriovenous shunt can, on rare occasions, be responsible for high-output heart failure and necrotizing cholangitis by arterial flow steal (the arterial supply of the biliary duct is exclusively dependent on the hepatic artery) [20]. Livers in patients with HHT may show either diffuse or partial hepatocellular regenerative activity, leading to regenerative focal nodular hyperplasia (FNH; Fig. 13A–D). The prevalence of FNH in patients with HHT is 100-fold greater than in the general population and can lead to dangerous hepatic biopsies. The combination of fibrosis (around abnormal vessels), nodular regenerative hyperplasia, and portal hypertension may lead to a misdiagnosis of cirrhosis [11]. Occasionally, patients with HHT present with true cirrhosis (secondary to extensive necrotizing cholangitis), hepatocarcinoma, or hemobilia (secondary to a MAV rupture in the biliary system). Angiomas can also coexist with telangiectases and hepatic MAV. Rarely, pancreatic telangiectasis can be associated with liver lesions (Fig. 14).

Transarterial embolization of liver arteriovenous fistulas has been performed but fatal outcomes due to necrotizing cholangitis suggest caution in its use. Orthotopic liver transplantation may represent the only definitive curative option for hepatic vascular malformations in HHT, even though at this time relapse has been observed in 2 of 28 patients undergoing transplantation [17].

Recurrent upper or lower gastrointestinal bleeding occurs in approximately 20% of patients with HHT and is responsible for anemia. The risk of fatal bleeding is mostly due to intestinal mucosal telangiectasis predominating in the gastroduodenal region, and less, frequently to intestinal AV shunt or angiodysplasia. Classical imaging techniques are limited. Only large AV malformations can be diagnosed on CT scan. The technique of capsule endoscopy is emerging to study the small bowel. Endoscopy is the gold standard for diagnosis and therapy of gastroduodenal and colonic telangiectases [21].

In summary, knowledge of genetic findings and of phenotypes leads to optimal management of the patient and family. In these patients, diagnosis and adequate therapeutic choice, with a multidisciplinary approach, can prevent serious complications and avoid the need for hepatic biopsies in the case of hepatic involvement.