Seong-Eun Kim1, J Scott Scott McNalley1, Adam de Havenon 2, Dennis L Parker1, and Gerald S Treiman 3
1UCAIR, Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT, United States, 2Department of Neurology, University of Utah, Salt Lake City, UT, United States, 3Department of Veterans Affairs, VASLCHCS, Salt Lake City, UT, United States
Synopsis
The purpose
of this work was to develop a 3D BB ME T2* Imaging technique to to allow quantitative ferumoxytol imaging
on delayed scans by measuring T2* in intracranial atherosclerotic
plaque(ICAD). Post-gadoliniun
enhancement 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. We
developed a 3D BB ME T2* imaging technique to allow quantitative ferumoxytol imaging
on delayed scans by measuring T2* in ICAD.
Purpose
Vessel wall MRI(vwMRI) has been used to detect
vulnerable plaque features including post-gadoliniun enhancement (PGE) in Intracranial
atherosclerotic disease(ICAD), with increased stroke risk independent of stenosis1.
PGE may be related to endothelial dysfunction or breakdown, leading to contrast
leakage into the vessel wall or secondary to plaque inflammation and
recruitment of leaky plaque neovessels2,3. The MRI contrast agent
ferumoxytol is taken up by macrophages in vivo and has been studied in carotid
atherosclerosis4,5. Ferumoxytol is an ultrasmall superparamagnetic iron-oxide(USPIO),
and results in decreased signal on T2*-weighted sequences in areas of accumulation6.
Delayed ferumoxytol imaging allows intravascular clearance with retention in the
macrophages present in vulnerable atherosclerotic plaque7. The purpose of this
work was to develop a 3D Black Blood(BB) Multi Echo(ME) T2* imaging technique to
allow quantitative ferumoxytol imaging on delayed scans by measuring T2* in intracranial
atherosclerotic plaque. Methods
The 3D BB ME T2* imaging sequence was implemented
with a quadruple inversion recovery (QIR) preparation8 and segmented
spoiled fast low angle shot (FLASH) readout. QIR prep was performed with two
sets of nonselective and slice selective hyperbolic secant adiabatic inversion
RF pulses to provide uniform blood suppression on the imaging slab. After each QIR
preparation, a series of multi echo(ME) FLASH measurements were acquired. Fig 1 demonstrates the pulse
diagram. MRI was performed on patients with
known ICAD using 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. 3D ME T2* images were acquired before (baseline)
and 72 hours after ferumoxytol injection (72h delay). The imaging parameters
for 3D BB ME T2* imaging were: transverse plane, in plane resolution=0.6 mm,
slice thickness=1.0 mm, 48 slices/slab, TI1/TI2 =300/200
ms, TEmin/ TEmax /TR =2.8/27.2/800ms, and DTE=3.4ms with 8 echoes. Total imaging time was
4 min 20 sec. T2* maps were created and displayed using homemade Matlab
software. T2* was calculated with least-square estimation
based on the semi-log linear regression of the signal values from all echoes
and their corresponding echo time according to: $$\frac{1}{T2^{\star}}=-\frac{lnS_{l}-lnS_{m}}{TE_{l}-TE_{m}}$$ where Sl, Sm are signal intensity at the echo time TEm, TEl ,respectively. Results
Figure 2 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
2a) shows severe left MCA M1 segment stenosis. Transverse
3D SPACE shows PGE in a left MCA stenotic plaque (white arrow) (Fig 2b). T2*
images with TE of 16.2 ms are shown on Fig 2e (baseline) and Fig 2f (72h delay).
Baseline T2* imaging shows no T2* signal in the left M1 plaque (white arrow,
Fig 2c). However, the 72 h delayed T2* image shows hypointense signal (white
arrow, Fig 2d). Baseline and 72h delayed T2* maps were calculated from the eight
echo T2* images acquired from the baseline and 72h delayed scans. 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 72h delayed scans. Mean T2* values of baseline and
72h delayed on the left M1 plaque were measure as 57.27±9.25 ms (Fig 2e) and 25.23±6.15
ms (Fig 2f), respectively. Discussion
Previous studies of iron nanoparticle uptake
have used 2D techniques, which are adequate for larger caliber arteries, larger
plaques and more 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. QIR preparation is a T1 insensitive blood
suppression technique and has been used for 2D post-contrast vwMRI. The larger slab
size in 3D acquisition, the more difficult it is to perfect the QIR and this
may result in imperfect blood suppression. When a relatively thin slab (48 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 intensities9.
To minimize those factors, R2*(1/T2*) can be used to assess the localization
and amount of uptake more directly and with high sensitivity.Conclusion
3D BB
ME T2* imaging can detect and quantify USPIO uptake in symptomatic ICAD, which
may provide important
mechanistic implications for the pathophysiology of PGE.Acknowledgements
: Supported by R01 HL127582,
RSNA Research Scholar Grant RSCH1414, AMAG Pharmaceuticals, American Heart
Association 17SDG33670114, Siemens
Medical Solutions, the Clinical Merit Review Grant from the Veterans
Administration health Care System. References
1. de Havenon
A, Chung L, Park M, et al. Intracranial vessel wall MRI: a review of current
indications and future applications. Neurovascular Imaging 2016;2(10).
2. Celletti FL, Waugh JM, Amabile PG, et
al. Vascular endothelial growth factor enhances atherosclerotic plaque
progression. Nature medicine 2001;7(4):425-429.
3. Libby P, Ridker PM, Maseri A.
Inflammation and atherosclerosis. Circulation 2002;105(9):1135-1143.
4. Trivedi RA, Mallawarachi C, U-King-Im
J-M, et al. Identifying inflamed carotid plaques using in vivo USPIO-enhanced
MR imaging to label plaque macrophages. Arterioscler Thromb Vasc Biol
2006;26:1601–6.
5. Tang TY,
Howarth SPS, Miller SR, et al. The ATHEROMA (Atorvastatin Therapy: Effects on
Reduction of Macrophage Activity) Study: Evaluation Using Ultrasmall
Superparamagnetic Iron Oxide-Enhanced Magnetic Resonance Imaging in Carotid
Disease. J Am Coll Cardiol 2009;53:2039–50.
6. Weinstein JS, Varallyay CG, Dosa E, et
al. Superparamagnetic iron oxide nanoparticles: diagnostic magnetic resonance
imaging and potential therapeutic applications in neurooncology and central
nervous system inflammatory pathologies, a review. J Cereb Blood Flow Metab Off
J Int Soc Cereb Blood Flow Metab 2010;30:15–35.
7. Alam SR, Stirrat C, Richards J, et al.
Vascular and plaque imaging with ultrasmall superparamagnetic particles of iron
oxide. J Cardiovasc Magn Reson 2015;17:1–9.
8. Yarnykh VL, Yuan C. T1-insensitive flow
suppression using quadruple inversion-recovery. Magn Reson Med. 2002
Nov;48(5):899-905.
9. Fayad ZA, Razzouk, Briley-Saebo KC et
al. Iron oxide magnetic resonance imaging for atherosclerosis therapeutic
evaluation: still rusty?. J Am Coll Cardiol. 2009 Jun 2; 53(22): 2051–2052.