Arterial Spin Labeling Measured Choroidal Blood Flow is Reduced in Age-Related Macular Degeneration and Correlates with Severity Level
Weiying Dai1,2, Lauren O’Loughlin1, Gina Yu3, Li Zhao1, David Alsop1, and Jorge Arroyo3

1Radiology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA, United States, 2Computer Science, State University of New York at Binghamton, Binghamton, NY, United States, 3Opthalmology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA, United States

Synopsis

Age-related macular degeneration (AMD) has been associated with reduced choroidal blood flow. However, current methods do not provide spatial location of reduced choroidal blood flow. Here we explored the feasibility and capability of arterial spin labeling (ASL) magnetic resonance imaging (MRI) in observing reduced choroidal blood flow in AMD patients and the association with their severity levels. Choroidal blood flow was significantly reduced in patients with AMD compared to controls. Most importantly, choroidal blood flow was significantly correlated with the severity levels of AMD. This suggests that ASL may be a useful tool to study the role of choroidal blood flow in the pathogenesis of AMD.

Purpose

Age-related macular degeneration (AMD) has been found to be associated with decreased choroidal perfusion (1,2,3,4). However, the current methods of measuring choroidal blood flow do not provide a global view of choroidal blood flow. We assessed choroidal blood flow in AMD patients using arterial spin labeling (ASL) magnetic resonance imaging (MRI) in a prospective, observational study to examine whether patients with AMD have significantly reduced choroidal blood flow and whether the severity levels of AMD patients are associated with their choroidal blood flow.

Methods

Eighteen subjects aged 71 years and older were divided into five groups: healthy volunteers (12 eyes from 6 patients), mild dry AMD (5 eyes from 3 patients), moderate dry AMD (7 eyes from 4 patients), severe dry AMD (6 eyes from 4 patients), and wet AMD (6 eyes from 4 patients). Each patient underwent a non-contrast enhanced brain MRI to measure choroidal blood flow using pseudo-continuous arterial spin labeling (PCASL) technique (5). A labeling duration of 3.75s and post-labeling delay of 1.25s were used. PCASL images were acquired with a 3D stack of spirals RARE sequence. 3D PCASL images covered the whole eyeball with a total of 12 slices (slice thickness of 4mm). Reference images were acquired with the same resolution as the ASL images to quantify the choroidal blood flow. Regions of interest were drawn as a rectangular box (containing 5´2 voxels) on the choroid of each eye. Paired t tests were used to compare the choroidal blood flow difference between controls and patients. Both left and right eyes were considered as independent samples in the t tests. A general linear model was built to evaluate the correlation between severity levels and choroidal blood flow by including age, gender and within-subject effect of left and right eyes from the same subject.

Results

Choroidal blood flow was significantly reduced in patients with AMD compared to controls (Fig. 1, mean reduction [MR] of 30.6%, p<0.01). Significance was also preserved in mild dry AMD (MR of 39.9%, p = 0.02), severe dry AMD (MR of 39.2%, p=0.02), and wet AMD (MR of 31.2%, p=0.03) compared to controls. Moderate dry AMD blood flow compared to controls was not found to be significant (16.2%, p=0.18). From the general linear model, choroidal blood flow was significantly associated with the severity levels of AMD (p=0.0397), age (p<0.0001) and gender (p=0.0065).

Discussions

MRI analysis of blood flow in patients with varying AMD severity confirmed blood flow is significantly reduced in patients with AMD versus control patients. Importantly, choroidal blood flow is significantly correlated with the severity levels of AMD. This suggests that choroidal blood flow may be used as a biomarker for the diagnosis of AMD. This finding could have important implications in AMD diagnosis and treatment research, and outlines how MRI could provide an accurate method of evaluating choroidal blood flow in patients at risk for AMD or other disorders with similar pathogenesis.

Acknowledgements

No acknowledgement found.

References

1. Tatyana I. Metelitsina, Juan E. Grunwald, Joan C. DuPont, Gui-Shuang Ying, Alexander J. Brucker, and Joshua L. Dunaief. Foveolar Choroidal Circulation and Choroidal Neovascularization in Age-Related Macular DegenerationInvest Ophthalmol Vis Sci. 2008;49:358–363) DOI:10.1167/iovs.07-0526

2. Fumihiko Mori, Suguru Konno, Taiichi Hikichi, Yuji Yamaguchi, Satoshi Ishiko, Akitoshi Yoshida “Pulsatile ocular blood flow study: decreases in exudative age related macular degeneration”, Br J Ophthalmol 2001;85:531-533 doi:10.1136/bjo.85.5.531

3. Juan E. Grunwald, Tatyana I. Metelitsina, Joan C. DuPont, Gui-Shuang Ying, and Maureen G. Maguire. Reduced Foveolar Choroidal Blood Flow in Eyes with Increasing AMD Severity. Opthalmology & Visual Science. 46(3) 1033-1038, 2005.

4. Thomas L. Berenberg, Tatyana I. Metelitsina, Brian Madow, Yang Dai, Gui-Shuang Ying, Joan C. DuPont, Lili Grunwald, Alexander J. Brucker, and Juan E. Grunwald. Retina. 2012 January ; 32(1): 25–31. doi:10.1097/IAE.0b013e3182150483.

5. W. Dai, D. Garcia, C. Bazelaire, D. C. Alsop, 2008. Continous Flow Driven Inversion for arterial spin labeling using pulsed radiofrequency and gradient fields. Magnetic Resonance in Medicine 60(6): 1488-97.

Figures

Fig. 1. The mean ASL image and reference image over 12 slices from an AMD patient (left eye: mild dry, right eye: wet) and a normal control.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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