The observational literature describing imaging characteristics of VAD is heterogeneous and of limited quality. Studies reviewed took varied approaches to patient selection and imaging, used different or inadequately described image acquisition methods, failed to adequately define radiographic signs or measure their inter-rater reliability, and lacked appropriate control or comparison populations. Results were highly variable across studies, and it is impossible to discern whether these differences were due to sampling variation or bias in study design or reporting. Nevertheless, in this study we are able to provide aggregate estimates of the frequency of various imaging findings reported in VAD as well as pooled estimates of the relative sensitivity of various imaging modalities.
The most common imaging characteristic reported for VAD was nonspecific arterial stenosis in 51%, with only 15% of patients identified as having other patterns generally considered “direct” signs of VAD such as intimal flap or double lumen. Our sample is most likely biased towards more severe cases of VAD, so the true prevalence of intimal flap or double lumen may be even lower than our pooled estimate. The relative paucity of more “characteristic” findings compared to traditional teaching4
may reflect the fact that our systematic review excluded studies where subjects were recruited solely based on imaging characteristics. Also, some of the clinico-radiographic VAD diagnoses might have been incorrect (e.g., atherosclerosis rather than VAD), diluting the measured frequency of more classic findings. There was wide variation in reported signs across studies. The heterogeneity may partly result from random variation due to small sample size in most studies; nevertheless, it raises questions about whether image interpretation of various radiographic signs was consistent. Whether multiple radiographic findings in a given vessel or holistic interpretation of images across imaging modalities in the same patient contributed to the final diagnosis could not be assessed. None of the included studies assessed the specificity of any individual imaging sign for the diagnosis of VAD in an appropriate comparison population. The extent to which detecting or correctly interpreting any of these radiographic signs of VAD might have been dependent on training background or experience remains unknown, although common interpretive pitfalls5
and subtle variations6
have been described.
Although conventional angiography was the most frequently reported confirmatory imaging modality, it is possible that a form of publication bias played a role, leading to a greater likelihood of a report on imaging findings in VAD when the diagnosis was confirmed by what is generally considered to be the gold standard (i.e., conventional angiography). In current clinical practice, use of routine conventional angiography to “rule out” or “rule in” VAD is probably infrequent. This might lead to the exclusion of studies where conventional angiography was negative, but a dissection was seen using another technique, such as MRI of the neck with fat-suppression images, which could bias the results. Only a few studies offered direct comparisons between two or more imaging modalities. CTA had the highest sensitivity (100%) relative to conventional angiography, with MRA and duplex missing about one in five cases of VAD. The greater concordance between conventional angiography and CTA is probably not surprising given the mechanistic similarity of these two luminal imaging techniques. None of the included studies assessed the specificity of any imaging modality for the diagnosis of VAD in an appropriate comparison population.
The sensitivity of CTA for symptomatic VAD appears to be high. Although we found only two studies reporting on a total of 32 patients, there were no reported cases in which CTA was deemed falsely negative (i.e., a patient diagnosed with VAD clinically and with radiographic evidence by conventional angiography but in which the CTA was normal). Limited sample size, diagnostic misclassification, and patient selection may account for the apparent perfection, however, since there is reason to believe that luminal imaging techniques miss small dissections with intramural hematomas that do not reduce lumen diameter. A recent radiographic database study found six cases of VAD (5 symptomatic, 3 with stroke) where the CTA was normal save for increased wall thickness (“suboccipital rind” sign) beyond that seen in a radiographic control population.6
In that study, conventional angiography results were reported in only one patient and said to demonstrate a “relatively normal lumen;” the authors cautioned against the use of any exclusively lumen-diameter-based technique (including conventional angiography) to rule out VAD.6
One small series in trauma patients suggests CTA may have low sensitivity for detecting asymptomatic blunt vertebral injuries (3 of 8 cases missed) relative to conventional angiography,7
perhaps because of imaging artifacts near the base of skull.5
Occasional false negative CTA interpretations have been reported for various other technical reasons.5
Together, these results cast some doubt on the use of either conventional angiography or routine CTA as the definitive diagnostic gold standard in VAD. Nevertheless, given the relatively lower sensitivity of other non-invasive techniques, CTA may still be the preferred initial imaging test for screening patients with suspected VAD.
The relatively lower sensitivity of MRI and MRA for VAD found in this review must be interpreted with some caution, since imaging protocols may influence overall sensitivity. For example, MRI of the neck with fat suppression is believed to detect VAD with greater sensitivity than MRA alone, and optimized imaging protocols have been proposed.8, 9
Unfortunately, included studies generally did not provide details about sequences used for MRI and MRA imaging; suboptimal imaging protocols could have artificially reduced the measured sensitivity of the technique. Nevertheless, false negative MRI and MRA findings in dissection are well described.5
Whether newer techniques such as diffusion-weighted imaging10
or high-field MRI11
will improve the sensitivity for VAD detection remains unknown.
The overall specificity of any imaging technique for symptomatic VAD, including conventional angiography, remains virtually unstudied. False positive MRIs, MRAs, CTAs, and duplex scans have all been reported.5, 12
Whether findings of luminal imaging techniques alone should be considered confirmatory of VAD remains controversial. Some authors contend that only techniques which image the vessel wall and demonstrate intramural hematoma are definitive for dissection, since most forms of luminal stenosis are nonspecific with regard to underlying pathology.8
The primary limitations of this analysis are the modest quality and heterogeneity of the primary data. All included studies were rated as medium or low quality methodologically (described in the accompanying manuscript). Individual studies generally failed to provide clear VAD definitions, adequate descriptions of patient recruitment and imaging protocols, and consistent measures of image interpretation or qualifications of readers. It is therefore unknown how many clinico-radiographic diagnoses might have been incorrect and whether this sample is reasonably representative of all symptomatic VAD patients. Virtually all data types were reported with wide variation across studies. Since final clinico-radiographic diagnoses were used as the gold standard, and diagnostic standards differed across studies, the measured relative sensitivities of particular imaging modalities could be biased. In addition, because we demanded at least some form of radiographic confirmation for VAD in our review, it remains unknown whether some patients with true VAD might have completely normal (falsely negative) vascular imaging.
Despite these limitations, we feel that this analysis provides useful information about the relative sensitivity of different imaging techniques, emphasizing the potential role of CTA as the most promising, non-invasive alternative to conventional angiography in screening for VAD (). It also indicates the relatively low frequency of certain “classic” radiographic findings, such as an intimal flap or double lumen; this emphasizes to the clinician that the lack of these findings should not eliminate the diagnosis of VAD as a possibility.
Figure 3 Flow chart showing suggested diagnostic process in evaluating a patient with potential vertebral artery dissection. Imaging should be evaluated for “direct” findings (double lumen, intimal flap) or “indirect” findings (arterial (more ...)
Future studies should compare imaging techniques in well-defined, undifferentiated populations of clinical VAD suspects (e.g., emergency department patients with dizziness or vertigo in association with head or neck pain). Imaging protocols should be standardized. Radiographic interpretation of pre-defined signs should be masked, and inter-rater reliability should be measured. Final clinico-radiographic diagnoses should be adjudicated by multi-disciplinary consensus according to clear criteria that also define the degree of diagnostic certainty. Such studies will permit robust measures of sensitivity, specificity, and likelihood ratios for each of the relevant diagnostic modalities in order to assess their potential clinical utility and offer more specific guidance to clinicians.