Seong-Eun Kim1, J Scott McNally1, Matthew Alexander1, Dennis L Parker1, Bradley D Bolster Jr2, Gerald S Treiman3,4, and Adam de Havenon5
1UCAIR, Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT, United States, 2Siemens Healthcare, Salt Lake City, UT, United States, 3Department of Surgery, University of Utah, Salt Lake City, UT, United States, 4Department of Veterans Affairs, VASLCHCS, Salt Lake City, UT, United States, 5Department of Neurology, University of Utah, Salt Lake City, UT, United States
Synopsis
Post-gadoliniun enhancement(PGE) in
ICAD may be related to endothelial dysfunction or breakdown or secondary to
plaque inflammation. Delayed ferumoxytol imaging allows intravascular clearance
with retention in the macrophages present in vulnerable atherosclerotic plaque. A 3D BB ME
T2* Imaging technique allows the quantitative ferumoxytol imaging on delayed
scans by measuring T2* in intracranial atherosclerotic plaque. We performed 3D BB T2* sequences on
ten patients with ICAD and measured T2* changes between baseline and 72 hour
after ferumoxytol injection. The iron nanoparticle uptake in symptomatic ICAD
presented in this work may provide important mechanistic implications for the
pathophysiology of PGE.
Purpose
Vessel wall MRI (vwMRI) has been used to detect vulnerable plaque
features including post-gadoliniun enhancement (PGE) in intracranial
atherosclerotic disease (ICAD), with stroke risk independent of stenosis1.
In the carotid artery, plaque enhancement correlates with both inflammation and
neovascularization2. PGE may
be related to endothelial dysfunction or breakdown, leading to contrast leakage
into the vessel wall or to plaque inflammation and recruitment of leaky plaque neovessels3,4.
Previous studies found significantly more macrophages in the symptomatic ICAD. Ferumoxytol
uptake by macrophages has been reported only in carotid atherosclerosis5,6.
Delayed ferumoxytol imaging allows intravascular
clearance with retention in the macrophages present in vulnerable
atherosclerotic plaque7. We developed
a 3D Black Blood (BB) Multi Echo (ME) T2* imaging technique to allow quantitative ferumoxytol uptake in intracranial atherosclerotic
plaque by calculating T2*8.Methods
With IRB consent, we recruited ten stroke
patients, four females and six males with age ranges from 39 to 80. All studies
were performed on a Siemens Verio 3T MRI scanner with 20 channel head coil. To
locate PGE in vessel wall, 3D T1w SPACE with DANTE preparation was performed.
We found eight MCAs and four vertebra arteries that showed the post enhancement. 3D ME
T2* images were acquired before (baseline) and 72 hours after ferumoxytol
injection (delayed). Table 1 summarizes the protocol. Baseline and delayed T2* maps
were calculated from the eight echo T2* images acquired from 3D ME T2* study. All images, including T2* maps, were registered to
the PGE to to confirm overlap of the PGE and ferumoxytol uptake using by the
custom software developed in Matlab. Results
The baseline
and delayed T2* measurements from ten patients are summarized on Table 2. Delayed
measurements compared to baseline PGE had overall lower plaque T2*
values. Figure 1 shows
results from a 79 year old female patient who was found to have multiple
acute infarcts in the left MCA distribution. A CTA MIP (Fig 1a) shows severe
left MCA M1 segment stenosis. 3D
SPACE shows PGE in a left MCA stenotic plaque (white arrow) (Fig 1b). Baseline T2*
imaging (5th echo with TE=16.2ms, Fig 1e) shows no T2* signal in the
left M1 plaque (white arrow, Fig 1c) comparing to the 72 h delayed T2* image (Fig
1f) which shows hypointense signal (white
arrow, Fig 1d). The 72h delayed T2* map (Fig 2d) shows a lower T2* value corresponding
to the T2* signal enhanced area. The black arrows on T2* maps show that the ferumoxytol
uptake after 72h post injection can be quantified by the difference in T2*
values measured from baseline and delayed scans. Mean T2* values of baseline
and delayed on the left M1 plaque were measured to be 57.27±9.25 ms (Fig 1e)
and 25.23±6.15 ms (Fig 1f), respectively. Fig 2 shows the results from a 72
year old female patient with bilateral PGE in V4. 3D DANTE post sequence (b)
shows the vessel wall enhancement surrounding V4 segments of the arteries with
single puncuate focus diffusion restriction. T2* images are shown on Fig 2c
(baseline) and Fig 2e (delayed). Mean T2* values of baseline and delayed on the
V4 were measure as 47.25±16.23 ms(Fig 2d) and
24.12±9.5 ms(Fig 2f), respectively. Discussion
T2* weighted
imaging often suffers from macroscopic susceptibilities that arise from the
sinus/brain interface. Image post-processing methods have been proposed to
correct T2* induced by macroscopic susceptibilities9. Previous studies of iron nanoparticle
uptake have used 2D techniques, which are adequate for larger caliber arteries,
larger plaques and linear segments such as the carotid6,7. For the
unique challenges inherent to ICAD, we developed a 3D BB ME T2* sequence that has
excellent blood suppression. When a relatively thin slab (36 mm) is used with 3D
acquisition and QIR preparation, we found good blood suppression on 72h delay
MRI. Delayed ferumoxytol T2* imaging has been used for
semi-quantitative measurement of uptake, but it can easily over- or under-estimate
the uptake caused by the differences in subject and coil positioning between
baseline and delayed scan which can influence the T2* signal intensities10.
To minimize those factors, T2* can be used to assess the localization and
amount of uptake more directly and with high sensitivity. Our measurements of
iron nanoparticle uptake in symptomatic ICAD have important mechanistic
implications for the pathophysiology of PGE. Further research will clarify if
this uptake is only seen in ICAD with PGE and if it is predictive of stroke
recurrence.Acknowledgements
Supported by R01
HL127582, NIH S10OD018482, RSNA Research Scholar Grant RSCH1414, AMAG Pharmaceuticals, American
Heart Association 17SDG33670114, Siemens
Medical Solutions, and the Clinical Merit Review Grant from the Veterans
Administration health Care System.
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