High resolution 3D IV-FSE enables differences between T1W and T2W images to be observed in LE-PVBG wall area in vivo
as early as 1 month post-implantation (6
). Furthermore, follow-up imaging in one patient has demonstrated changes of the wall area between 1 and 6 months post-implantation with either contrast weighting (18
). The current study quantified those differences in LE-PVBGs imaged six months after implantation, in six patients with no clinical evidence of graft failure. The observed mean difference in vessel wall area was found to be significant and corresponded to a difference of 0.32 ± 0.12 mm in average vessel wall thickness (). Furthermore, the difference was entirely attributable to an enlarged outer vessel wall boundary in all T1W images compared to their T2W counterparts. This result remained significant even after accounting for a systematic negative bias in the lumen area measured from T2W images.
Prior studies of native arteries, specifically in carotid endarterectomy specimens (7
), indicate that at 9.4 - 11.7 T the media has a longer T2
(70 - 76 ms (28,30)) than fibrous tissue (40 - 60 ms), and that relative differences in T1
relaxation rates between these components are less pronounced (28
). This led us to believe that the difference in wall area observed in vivo
between the two contrasts in LE-PVBGs is primarily due to the differing T2
properties of the neo-intima/media versus the adventitia. While T2
rates are expected to be longer at lower field strengths, conflicting measurements have been reported for the carotid media (40 - 60 ms) at 0.5 - 1.5 T (7
). This is also confounded by the fact that LE-PVBGs have a different tissue composition than native arteries, and T2
rates of wall tissue may also vary during graft maturation due to changes in composition. We previously described early lumen dilatation (0-1 month) followed later by stiffening of the vein graft wall (3-6 months) (5
). This suggests significant deposition of fibrous protein during the later phase of vein graft maturation, which is likely to be accompanied by changes in T2
To directly assess whether wall area differences observed in vivo may indeed be driven by differing T2 rates in the two LE-PVBG wall layers, ex vivo T2 relaxometry studies were performed in two fresh LE-PVBG specimens immersed in saline at room temperature. Care was taken to match all other experimental conditions, and both specimens were excised at similar post-implantation times as those grafts imaged in vivo. In agreement with previous studies we also found a significant mean difference of 122.1 ms between the T2 relaxation rate of the neo-intimal/medial (T2 of 174.7 ± 12.1 ms) versus the adventitial (T2 of 52.6 ± 3.5 ms) tissue, as determined by correlative histology. We believe this difference sufficiently accounts for the in vivo observation of differing vessel wall area; the slow decay of signal from tissue in the neo-intima/media may render it hyper-intense in either contrast weighting. In contradistinction, signal from the adventitia may persist at the short TE of the T1W images (17 ms) but would vanish at the longer TE of the T2W images (60 ms).
Accordingly, we hypothesized that the outer wall boundary determined from in vivo
T2W images extends only to the neo-intima/media, while that identified in T1W images includes the adventitia. This would explain the significant difference in vessel wall area between contrasts. To indirectly test this hypothesis, we compared the signal intensities of the two vessel wall layers in T1W images. Under idealized assumptions, we found that the signal intensity ratio between these two layers was RT1W
= 0.84 ± 0.09 (CNRT1W
= 1.19 ± 0.13) in the in vivo
T1W images, in excellent agreement with its predicted value of 0.8 based on the ex vivo
rates and the effective TE used for T1W imaging. In comparison, for the in vivo
T2W images the expected signal loss is predicted to be relatively larger with a ratio of
, thereby rendering the outer layer less likely to be perceived as part of the vessel wall.
This work presents a number of methodological limitations. The significance of the in vivo
observation of differing wall areas necessitated accounting for the small bias in lumen area observed between contrasts. Ideally, one would expect lumen area to be independent of contrast weighting. However, at the spatial resolutions achieved here there are two likely explanations for such a bias. First, the media may be more blurred into the lumen due to the longer echo train duration used for T2W as opposed to T1W imaging (ETL of 18 vs 12, echo train duration of 210.6 ms vs 91.2 ms) (35
), thereby reducing the perceived area of the lumen. Second, it is possible that differences in blood nulling between contrasts can lead to this discrepancy. A combination of these effects is also possible.
Another potential limitation stems from the assumptions used to correlate the in vivo
T1W wall layer signal intensities ratio with that predicted from the ex vivo
measurements. The assumption of similar proton density appears reasonable given the small signal intensity differences throughout the vessel wall at a short TE (c.f., ). It is also known that T2
rates of vessel wall tissues become slightly elongated (5%-20%) at room temperature as opposed to body temperature (33
). Hence, one would expect a slightly lower signal intensity ratio in vivo
than that predicted using ex vivo
measurements Additionally, T1
weighting effects in LE-PVBGs have not been studied, although previously reported differences in T1
rates are relatively small between layers (28
) and their effect is expected to be limited.
It may also be argued that the use of fat saturation renders the outer boundary necessarily smaller in T2W images than that available from the high contrast between the outer vessel wall boundary and surrounding fat in the T1W images. The media-to-adventitia CNR in T1W images suggests that the two tissues are likely to be perceived as a single component. For the in vivo T2W images the higher CNR between the two layers suggests that they can be separated. However, while the SNR of both layers in T1W images is similar to that of the media in T2W images (approximately 9), the SNR for the adventitia given its faster relaxation rate is expected to be significantly lower in T2W images, approximately SNRAT2W = SNRMT2W × RT2W ≈ 3.9. In conjunction with the increased contrast, delineation of the outer wall would thus be much more problematic in T2W images than in T1W images with the current protocols. Thus, although the lack of fat saturation may have contributed to the perception of a larger vessel wall area in T1W images, the loss of outer wall layer signal in T2W images is an independent effect and should be detected even if fat saturation is applied to T1W images as well.
A final limitation is the lack of ex vivo measurements and histology for those LE-PVBGs imaged in vivo. While the segment imaged in one patient enrolled in this study exhibited significant intimal hyperplasia, it was not excised at revision, a common surgical practice. This limitation is exacerbated in the comparison of in vivo observations based on the ex vivo measurements. One of the two specimens was excised at 247 days postimplantation, 58 days longer than the mean graft maturation time for those patients imaged in vivo. However, the fact that measured T2 rates were statistically similar between specimens for both layers () supports this analysis.
Further enhancements in resolution will enhance our ability to differentiate the LE-PVBG wall layers, given the small thickness attributed to the adventitia. The method can be readily applied at 3 T to increase resolution. Additionally, the ETL can be extended to increase resolution while avoiding signal-to-noise reduction or scan time increase. However, in our experience, a longer echo train introduces significant blurring at the resolutions achieved here. This can be avoided by the use of variable flip angle refocusing, based on the expected tissue T1
relaxation rates (36
). At present, the influence of vein graft maturation on T2
is not known, nor is it known if differences would be significant in this context. Increased longitudinal graft coverage will also be important for future clinical studies. This can be achieved by trading the number of signal averages (NEX) used in this study for longitudinal coverage. However, we have found that the use of DIR blood-nulling limits our ability to image a segment longer than the 3.6 cm used here. Methods based on flow-induced dephasing (15
) can overcome this limitation.
In conjunction with prior studies encompassing earlier time-points and follow-up imaging (6
), the present data suggests that larger studies concentrating on different time points post-implantation using high-resolution multi-contrast 3D IV-FSE are likely to yield significant results regarding the relative remodeling of lower extremity vein graft wall layers during their adaptation to the arterial environment. Most of what is currently known about vein graft pathology is limited to specimens acquired either post-mortem (38
) or in animal models (39
). The ability to sequentially assess the relative remodeling of the neo-intima/media and the adventitia of the vein graft in vivo
would be of great value in understanding the biology of vein graft maturation, and the relationship with disturbances in biomechanics, and state of inflammation (34