MR Imaging of ARVCD

Among the current cardiac MR applications in cardiomyopathies, the greatest potential as well as biggest challenges are in the diagnosis of ARVC/D. MR imaging allows both qualitative and quantitative analysis of RV function [14]. MR has the ability to demonstrate intramyocardial fat [12] and recently, delayed enhancement MR imaging has been shown to be useful in detecting fibrosis in the RV in ARVC/D

[15]. The last 10 years have seen significant improvements in MR hardware, with tremendous increases in acquisition speed and image quality. ECG gating and breath-hold imaging have reduced motion artifacts and improved tissue contrast is achieved by inversion recovery black-blood imaging techniques

[16]. ECG gated steady state free precession imaging (SSFP) pulse sequences have resulted in better delineation of endocardial borders enabling accurate and reproducible volumetric measurements [14]. For these reasons MR imaging has been increasingly used for evaluation of the RV and has evolved as the non-invasive modality of choice in ARVC/D.

Casolo et al. [12] were the first to describe the use of MR imaging to assess ARVC/D in 1987. They demonstrated intramyocardial fat deposits in the RV on conventional spin echo imaging. Since that time several authors including our group have reported MR abnormalities in ARVC/D [17-26]. Broadly, MR imaging abnormalities in ARVC/D can be grouped into two major categories: (1) morphological abnormalities, and (2) functional abnormalities. Morphologic abnormalities include intramyocardial fat deposits, focal wall thinning, wall hypertrophy, trabecular disarray, and RV outflow tract enlargement. Functional abnormalities include regional contraction abnormalities,

Fig. 15.1 • Gradient echo image in the oblique sagittal plane showing the triangle of dysplasia, which consists of the inferior-sub tricuspid area (thick white arrow), RV apex (black arrow) and the RV infundibulum (thin white arrows). PA,pul-monary artery; RA, right atrium; RV, right ventricle

aneurysms, RV global dilation/dysfunction, and RV diastolic dysfunction. The sites of involvement of these abnormalities are observed in the "triangle of dysplasia," which consists of the inferior-sub tricuspid area, RV apex, and the RV infundibulum [1,27] (Fig. 15.1). The goal of MR imaging in ARVC/D is to accurately assess the RV for the presence or absence of these abnormalities to aid in the diagnosis and to assist in the management of patients.

MR Assessment of Cardiac Morphology in ARVC/D

Accurate depiction of morphology is very important in most cardiac applications and ARVC/D exemplifies this statement. Morphologic evaluation is generally performed by the use of "black-blood" techniques. Currently, black-blood techniques using breath-hold imaging with double inversion recovery fast-spin echo (DIR-FSE) techniques are preferred to traditional spin echo (SE) imaging. Breathhold FSE sequences consistently provide end-diastolic images with minimal motion artifacts and improve resolution of myocardial detail [28-30]. Black blood inversion-prepared, half-Fourier single-shot turbo spin echo (HASTE) imaging is currently not recommended due to blurring of myocardial detail with this sequence. A dedicated cardiac coil is recommended for best results, although we use only the anterior coil elements to prevent "wrap-around" artifact when using small field of view. An anterior saturation band (Fig. 15.2) is placed over the anterior subcutaneous fat for further suppression of motion artifacts.

Fig. 15.2 • Axial black blood image showing the location of anterior saturation band (arrow)

Morphologic Features of ARVC/D Intramyocardial Fat

Normal myocardium shows intermediate MR signal similar to skeletal muscle, and fat appears as a hy-perintense signal (bright) on black blood images. Figure 15.3a shows a black-blood MR image from a normal volunteer. In normal individuals epicardial fat overlies the RV, and is abundant towards the RV apex and in the atrio-ventricular groove. There is often a clear line of demarcation between the gray RV myocardium and the epicardial fat. Disruption of this line of demarcation (Fig. 15.3b) and extension of the hyperintense signals into the RV myocardium is frequently noted in ARVC/D, indicating infiltration of epicardial fat into the RV wall.

The prevalence of intramyocardial hyperintense MR signals in ARVC/D on Tl-weighted SE imaging has ranged from 22% to 100% in different studies [17-26]. The largest series is by Auffermann et al. [21] who imaged 36 biopsy-proven ARVC/D patients, and found intramyocardial hyperintense signals in only 22% of patients. The patients in this study had different stages of ARVC/D, and a significant number had localized ARVC/D. Fat infiltration on MR imaging predicted inducibility of ventricular tachycardia at electrophysiologic testing. Wichter et al. [22] added 16 additional patients to the series by Auffer-man (52 total patients) and concluded that patients with extensive ARVC/D had a higher incidence of fatty replacement of the RV compared to localized r

Fig. 15.3 • (a) Axial black blood image from a normal volunteer showing a clear line of demarcation between the epicardial fat and the underlying myocardium.Also note the abundance of epicardial fat in the atrio-ventricular groove (arrowhead) and at the apex (arrow). (b) Axial black blood image from a patient with ARVC/D showing lack of demarcation between epicardial fat and myocardium (arrows)

forms (96% vs. 58%). Menghetti et al. [26] described SE MR imaging findings in 15 ARVC/D patients diagnosed using the Task Force criteria and reported intramyocardial hyperintense signals in 62% of patients. The differences in incidence of fat signal in ARVC/D are largely based on differences in patient selection, as well as the definition of abnormal intramyocardial hyperintense signals. We used breath-hold DIR-FSE technique to evaluate intramyocardial fat in ARVC/D and found high intramyocardial T1 signal (fat) in nine of twelve patients (75%) who were prospectively diagnosed using the current Task Force criteria [17]. The use of spectrally selective fat suppression with the DIR-FSE sequence provided additional evidence of fat infiltration due to high contrast between epicardial fat and the RV myocardium. Fatty infiltration was more commonly noted in the basal regions (RV inflow and RV outflow) and less frequently at the RV apex (one out of nine patients).

Although fat infiltration on MR imaging is sensitive to the disease process, this finding is not specific. For example, we have recently observed a group of patients with marked lipomatous infiltration of the right ventricle, who did not otherwise meet Task Force criteria for ARVC/D (discussed further below). The etiology of RV fat in that group has not been determined. Fatty replacement of the myocardium has also been described as a sequela of myocardial infarction as well as nonischemic cardiomyopathies such as myotonic dystrophy. Finally, detection of in-tramyocardial fat on MR imaging requires considerable experience and over reliance on this finding alone may lead to misdiagnosis of ARVC/D.

Wall Thinning

RV wall thinning is defined as focal abrupt reduction in wall thickness to <2 mm, surrounded by regions of normal wall thickness. Wall thinning is thought to be due to progressive loss of epicardial and myocardial layers which leaves a thin rim of subendocardium that is usually spared. Wall thinning, often observed in pathologic specimens, was not observed in vivo until the emergence of MR imaging. Compared to in-tramyocardial fat, fewer reports have addressed the issue of wall thinning in ARVC/D. Aufferman et al. reported wall thinning in 67% of biopsy-proven ARVC/D patients on SE MR imaging [21]. In our series we found wall thinning in less than 25% of patients who met the Task Force criteria (Fig. 15.4). In our ex-

Fig. 15.4 • Fat suppressed axial black blood image from a patient with ARVC/D showing focal abrupt thinning (arrowheads) of the anterior wall of the right ventricle

a b perience wall thickness is often difficult to assess due to adjacent high epicardial fat signal, motion artifacts, and high blood signal in areas of RV trabeculations.

Wall Hypertrophy

Wall hypertrophy is defined as RV wall thickness >8 mm. This finding is seldom observed in pathologic specimens as the true RV myocardium is measured exclusive of the epicardial fat [31]. In vivo this differentiation is sometimes not possible due to extensive fibro-fatty infiltration with loss of distinction between epicardial fat and the true myocardium. In such cases the RV wall appears hypertrophied with MR images showing islands of gray muscle surrounded by bright signals compatible with fat. This finding was observed in five of the twelve patients (42%) of our series [17]. Use of fat suppression reveals multiple signal voids within the RV myocardium in locations that showed hyperintense signals in the nonfat-suppressed images (Figs. 15.5a, 15.5b).

Trabecular Disarray

Molinari et al. [25],were the first to describe giant Y-shaped trabeculae and hypertrophy of the moderator band in patients with ARVC/D. This finding has been equated to the angiographic finding of deep fissures with a "pile d'assiettes" (stack of plates) appearance. We found a prevalence (40%) of trabecu-lar hypertrophy and disarray, similar to that of the above study in ARVC/D patients. This finding is not specific for ARVC/D and may be present in any condition that results in RV hypertrophy or enlargement.

RV Outflow Tract Enlargement

The RV outflow tract (RVOT) is a common location for localized ARVC/D. The right ventricular outflow is usually equal to or marginally smaller than the aortic outflow tract at the level of the aortic valve. An exception to this rule concerns pediatric patients in whom the RVOT may be larger than the left ventricular outflow. The presence of an enlarged RVOT beyond adolescence is uncommon. Ricci et al. [23] reported an enlarged RVOT in 15 patients with ARVC/D compared to patients with dilated cardiomyopathy. More important than enlargement is a dysmorphic appearance of the outflow tract (Fig. 15.6). Abnormal appearance of the RVOT, which is dyskinetic in systole, is highly suggestive of ARVC/D in the absence of pulmonary hypertension or left to right shunts.

Fig. 15.5 • (a) Axial black blood image from a patient with ARVC/D showing heterogeneously increased T1 signal in the right ventricular anterior wall (arrow).(b) Fat suppressed image at the same level shows multiple signal voids in the same location of the hyperintense signals on the nonfat suppressed image (arrow)

Fig. 15.5 • (a) Axial black blood image from a patient with ARVC/D showing heterogeneously increased T1 signal in the right ventricular anterior wall (arrow).(b) Fat suppressed image at the same level shows multiple signal voids in the same location of the hyperintense signals on the nonfat suppressed image (arrow)

Fig. 15.6 • Axial black blood image from a patient with ARVC/D showing enlarged and dysmorphic outflow tract with focal bulging anteriorly (arrow)

MR Imaging Fibrosis in ARVC/D

One of the pathologic hallmarks of ARVC/D is fibrosis of the RV that accompanies fatty infiltration. My-ocardial delayed enhancement MR imaging allows for noninvasive detection of fibrosis in the RV that may improve the specificity of ARVC/D diagnosis. We imaged twelve ARVC/D patients with MDE-MR imaging. Eight (67%) out of the twelve ARVD/C patients demonstrated increased signal consistent with fibrosis in the RV [15]. There was excellent correlation with histopathology (Fig. 15.7). The areas of fibrosis on MR

imaging corresponded with regions of kinetic abnormalities. The extent of fibrosis showed an inverse correlation with global RV function. An important finding of our study was that 18 patients with idiopathic ventricular tachycardia who underwent MDE-MR imaging showed no evidence of fibrosis, highlighting the negative predictive value of MDE-MR imaging in evaluating patients with suspected ARVD/C. Presence of fibrosis detected on MDE-MR imaging predicted inducibility of sustained ventricular tachycardia during electrophysiologic testing, thus providing information regarding arrhythmic risk of such patients.

Fig. 15.7 • The top left and right panels show the end diastolic and systolic frames of a short axis cine MRI.There is an area of dyskinesia in the right ventricular free wall due to a focal aneurysm.The bottom left panel displays the delayed-enhanced MRI with increased signal intensity within the right ventricular myocardium,at the location of right ventricular aneurysms. The bottom right panel shows the corresponding endomyocardial biopsy.Trichrome stain of the right ventricle at high magnification shows marked replacement of the ventricular muscle by adipose tissue.The adipose tissue cells (arrowhead) are irregular in size and infiltrate the ventricular muscle. There is also abundant replacement fibrosis (arrow).There is no evidence of inflammation

Fig. 15.7 • The top left and right panels show the end diastolic and systolic frames of a short axis cine MRI.There is an area of dyskinesia in the right ventricular free wall due to a focal aneurysm.The bottom left panel displays the delayed-enhanced MRI with increased signal intensity within the right ventricular myocardium,at the location of right ventricular aneurysms. The bottom right panel shows the corresponding endomyocardial biopsy.Trichrome stain of the right ventricle at high magnification shows marked replacement of the ventricular muscle by adipose tissue.The adipose tissue cells (arrowhead) are irregular in size and infiltrate the ventricular muscle. There is also abundant replacement fibrosis (arrow).There is no evidence of inflammation

MR Assessment of Cardiac Function in ARVC/D

Cardiac function can be assessed by "bright-blood" techniques, derived from the appearance of intracavitary blood. Multiple consecutive images that are acquired with a high temporal resolution can be viewed dynamically to generate functional information. Ventricular volumes and masses using bright-blood imaging have been shown to be accurate and reproducible and MR imaging is considered the standard of reference [32, 33]. Although a number of MR sequences exist for bright-blood imaging, steady-state free precession imaging also termed FIESTA, true FISP, or Balanced Fast Field Echo is the preferred technique. SSFP sequences result in improved contrast between the blood pool and the myocardium compared to segmented k-space cine gradient echo images [34]. If SSFP is not available, segmented k-space cine gradient echo images (e.g., fast low angle shot - FLASH; fast cardiac gated gradient echo - FASTCARD) can be used. Conventional cine k- space GRE images rely on flowing blood to generate bright blood. In the dysfunctional RV, blood velocities are reduced and signal intensity decreases with conventional GRE imaging. With SSFP, the signal intensity remains high since the signal intensity is proportional to T2 time. There exists an excellent correlation between MR imaging and RV angiography [21], the latter being the former gold standard for RV function. For the above reasons MR imaging is a noninvasive alternative for RV functional assessment in screening of first-degree relatives for ARVC/D and also for follow-up.

Functional Abnormalities in ARVC/D

Global RV Dilation/Dysfunction

Fibrofatty replacement of the RV in ARVC/D eventually leads to RV dilation and dysfunction. RV dysfunction is often asymptomatic but is preceded by patient symptoms related to an associated arrhythmia. Aufferman et al. reported an increased RV end diastolic volume index in ten patients with ARVC/D who were inducible on electrophysiologic studies compared to control subjects [21]. The RV volume indices and the global function of ARVC/D patients, who were noninducible, did not differ from the control subjects, suggesting that the patients in this group had localized ARVC/D. Several other authors have reported RV enlargement and dysfunction using a variety of patient selection criteria. In our report we found that a majority of patients (75%) who met the Task Force criteria had some degree of RV enlargement and dysfunction at presentation. Also, there was a linear correlation between the RV end di-astolic volumes and the duration of symptoms, suggesting the progressive nature of the disease [17]. Serial quantitative volumetric assessment of RV may be important in assessing disease progression and may have an important role in evaluation of first-degree relatives.

Regional Dysfunction

Regional dysfunction is generally thought to be due to focal fibro-fatty infiltration that precedes changes in global ventricular function. RV angiography was traditionally used to evaluate this, but currently MR imaging has replaced RV angiography at our Institution due to its noninvasive nature.

Regional functional abnormalities of the RV described in ARVC/D include focal hypokinesis (wall thickening of <40%), akinesis (systolic wall thickening of <10%), dyskinesis (myocardial segment, which moves outward in systole), and aneurysms (segments with persistent bulging in diastole, and dyskinetic in systole). Studies have consistently reported high incidence of regional dysfunction in ARVC/D [17-27]. One study, which compared MR imaging to angiography, showed 86% correlation between the two modalities [21]. The areas of dysfunction corresponded to the areas of signal abnormality observed on black blood MR imaging. The presence of signal abnormality associated with abnormal wall motion is more suggestive of ARVC/D compared to either of them alone. In our series, 67% of the patients had regional contraction abnormalities that correlated to the area of adipose replacement on MR imaging. Of these patients, 50% had aneurysms localized to the region of adipose replacement. Less than 25% of the patients with a final diagnosis of ARVC/D had RV aneurysms. Care should be taken while interpreting RV regional function from axial views, as the axial plane is not orthogonal to the inherent axis of the heart and apparent bulging can be seen even in normal volunteers. Correlation with horizontal long-axis view may be helpful to avoid misinterpretation of RV regional function [35].

Diastolic Dysfunction

Few investigators have used MR imaging to assess diastolic function in ARVC/D. Aufferman et al. [21] were the first to use time-volume curves obtained from cine gradient-echo MR imaging to assess diastolic function in biopsy-proven ARVC/D patients. Comparison with control patients with ARVC/D had a significant delay in diastolic relaxation of the right ventricle. The same patients also had increased RV volumes and reduced function, so that diastolic relaxation may not provide additional diagnostic information. More recently Kayser et al. [36] evaluated diastolic function in 14 patients with ARVC/D with preserved systolic function using MR velocity mapping of transtricuspid flow. ARVC/D patients showed a significant decrease in peak filling rate and in the slope of the descending part of the early filling phase. The ratio of peak early filling rate to peak atrial contraction and ratio of integrated early filling to integrated atrial contraction (i.e., volume) were significantly lower in patients than in healthy volunteers. These data are consistent with studies using echocardiography, suggesting that diastolic abnormalities may precede systolic dysfunction and may have a role in early diagnosis.

Role of MR Imaging in Diagnosis of ARVC/D

The lack of a single diagnostic gold standard for ARVC/D makes it difficult to define the sensitivity and specificity of any single modality in diagnosing ARVC/D. MR imaging is unique, compared to other imaging modalities, due to its ability to depict in-tramyocardial fat. Bluemke et al. reported poor interreader reproducibility for detection of intramy-ocardial fat signal on conventional SE MR images

[37], raising an important issue in defining the role of MR imaging in ARVC/D using conventional (i.e., noncardiovascular) MR scanners. Although the interobserver reproducibility appears to be significantly better with improvements in image quality, it is important to realize that the presence of intramy-ocardial fat on MR imaging is not synonymous with ARVC/D. Isolated areas of fat replacement are not specific to ARVC/D and have been reported in elderly patients, patients receiving long-term steroids, and in other cardiomyopathies [38,39]. Discrete areas of fat substitution have also been reported in idiopathic ventricular tachycardia, which is an important differential diagnosis for ARVC/D [40-42]. Recently we [43] have observed marked lipomatous infiltration of the right ventricle in young nonobese individuals who were evaluated for nonsustained ventricular arrhythmias (Fig. 15.8). None of these patients had global or regional functional abnormalities and thus appeared to be a distinct group of patients defined by MR imaging that should be differentiated from patients with ARVC/D. However, the long term arrhythmic risk and the clinical course of such patients remains unknown.

Over-reliance on the presence of intramyocardial fat has in fact resulted in a high frequency of "misdiagnosis" of ARVC/D [44,45]. In our experience this finding alone is neither sensitive nor specific for the diagnosis. Our experience with MR imaging of autopsy hearts lead us to conclude that the achievable spatial resolution in current state-of-the-art clinical protocols substantially limits the capability to detect subtle RV intramyocardial fatty changes. Since the

Fig. 15.8 • 45-year-old female,with history of nonsustained ventricular tachycardia.(a) Axial proton-density-weighted, fast spin-echo MRI without fat saturation image shows fat replacement of the entire RV wall (darkarrows).The fatty replaced RV wall appears thickened. (b) Axial proton-density-weighted fast spin-echo MRI with fat saturation shows suppression of the fatty component of the RV wall. A thin portion of nonfatty RV wall is now seen (white arrows)

Fig. 15.8 • 45-year-old female,with history of nonsustained ventricular tachycardia.(a) Axial proton-density-weighted, fast spin-echo MRI without fat saturation image shows fat replacement of the entire RV wall (darkarrows).The fatty replaced RV wall appears thickened. (b) Axial proton-density-weighted fast spin-echo MRI with fat saturation shows suppression of the fatty component of the RV wall. A thin portion of nonfatty RV wall is now seen (white arrows)

disease is rare, most MR imaging centers have little or no experience with diagnosis of ARVC/D. Technical problems in imaging patients with arrhythmias, and lack of experience by imaging physicians suggest that MR imaging should be only one part of a comprehensive evaluation for these patients. MR imaging provides information related to RV size, global and regional function, and aneurysm formation that may be useful to delineate structural and functional abnormalities which could be used to assess these parameters for the Task Force criteria. Even using conventional SE imaging, the morphologic features appear to distinguish ARVC/D patients from normal individuals [44].

We find that MR imaging can reliably identify patients who require additional invasive testing. A completely normal MR study performed with good technique and evaluated by an experienced observer in patients with no abnormalities on electrocar-diography or echocardiography is reassuring, and such patients may not need invasive testing (an-giography/biopsy) in the absence of other clinical criteria. If signal abnormalities and wall motion abnormalities coexist, invasive testing should be undertaken to confirm the findings. Minor structural abnormalities, i.e., signal abnormalities in the absence of wall motion changes, present a challenge as the need for further evaluation of such patients is unclear. Adherence to Task Force criteria is recommended, and these "minor" criteria may not necessitate invasive testing. It should be recognized that ARVC/D Task Force criteria do not currently recognize fat signal on MR (or CT) as a diagnostic criterion for the disease.

Future Directions

If significant strides in MR technology over the last 10 years continue, MR imaging should emerge as a critical test for the diagnosis of ARVC/D.

A current limitation for black blood imaging is poor spatial resolution. Increases in spatial resolution result in longer and prohibitive breath-hold duration. One approach would be the use of navigatorecho gated techniques, which allow free breathing. This technique was initially described by Ehman and Felmlee in 1989 [46] and is currently used in coronary imaging. Navigator echoes are positioned over the right diaphragm and imaging is triggered when the diaphragm position is within a 4-5 mm window. In conjunction with 3 dimensional black blood techniques, this approach could improve spatial resolution for detection of intramyocardial fat. Limitations to this technique include increased scanning times (by a factor of two), increased edge blurring, and susceptibility to motion artifact in patients with irregular breathing patterns or those who have arrhythmia.

Another aspect of ARVC/D evaluation that needs improvement is regional function assessment. Myocardial tissue tagging provides accurate and quantitative data regarding regional function and may potentially improve the sensitivity of MR imaging to detect regional dysfunction in ARVC/D. Fayad et al. described this approach in the RV [47]. However, tissue tagging is not easily applied due to the very thin RV free wall and resultant poor signal-to-noise ratio.

Currently, two large clinical trials in ARVC/D patients are underway. The European ARVC/D registry [48] is attempting to prospectively validate criteria for clinical diagnosis of ARVD/C, evaluate the accuracy of clinical diagnosis, and assess the natural course of the disease. The Multidisciplinary Study of Right Ventricular Dysplasia (US ARVC/D study) [49] aims to prospectively enroll 100 patients with ARVC/D and 200 first-degree relatives and is attempting to develop quantitative methods to assess RV function to enhance the specificity and sensitivity of the diagnosis of ARVC/D. These studies may define the diagnostic role of MR imaging in ARVC/D as well as in family members.

Was this article helpful?

0 0

Post a comment